Rare Disease Discussions

Nicola Longo MD, PhD, and Mark Roberts, MDDrs. Longo and Roberts discussed the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025, and is intended for healthcare professionals only.This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas.In this part, Doctors Roberts and Longo will discuss treatment with gene therapies.Question: Can one administer AAV-mediated gene therapy repeatedly?Mark Roberts, MDI think the traditional view would have been no. One can think of gene therapy as a silver bullet. Hopefully, it will reach its target. But if it's not effective, that bullet has been shot, the immunological response has occurred, and it means redosing, at least with that particular vector, may become difficult. But this situation is changing and evolving as we have better understanding of immunological modulation for repeat testing. We were discussing this yesterday evening, weren't we, Professor Longo?Nicola Longo MD, PhDCorrect. Basically, the current AAV-based gene therapy cannot be readministered. It is either effective, or it doesn't work. The other thing is that even though in theory, one could utilize a different AAV vector with different immunogenicity, there is many times cross-reactivity among the different adenovirus, adeno-associated viruses. Now, there are approaches in animal models in which you give a strong immune suppression to prevent the creation of the immune response against the adeno-associated virus, and at least in the animal model, it has been possible to give some of the gene therapy repeatedly.The second approach that is being tested is with gene correction therapy, in which by using an RNA guide and the CRISPR/Cas9 system delivered by lipid nanoparticles, you basically correct some of the effective genetic information. Obviously, since this is done by lipid nanoparticles and not by an AAV, the immunity that you create is really not there. You can give this one repeatedly, and in theory, it can be given more than one time. But again, you are absolutely correct. The current gene therapy cannot be given twice, and either it works or it doesn't work.Question:vWill gene-therapy-treated patients be able to go back to the standard of care or enzyme replacement therapy?Mark Roberts, MDI think when we're talking to patients about the potential benefits of gene therapy and the amelioration of the requirement to have these infusions on a regular basis of ERT, the hope is that will work, but they need to be reassured that we can potentially go back to the ERT. Gene therapy is an important treatment, but we don't know the destination of the patient at the beginning, and we have to make it available to them to go back to ERT.One of the crucial questions, of course, though, is the basis of the immunological reaction that perhaps prevented the gene therapy being effective. If it's against the viral vector, well, okay. If it's against the transgene, not great. If it's against the functional protein, that becomes more difficult. It is somewhat, I think at this time, to be fair to say to patients, think of gene therapy as a trial treatment. It is somewhat a leap of faith and an important observation, of course, for the patient community, but just be aware there may be downsides.Nicola Longo MD, PhDThey totally agree with Dr. Roberts. In general, they should be able to go back to enzyme replacement therapy if the gene therapy is not effective. However, what we are starting to appreciate is that we need to understand the immune response, not just to the enzyme replacement therapy, but also to gene therapy. What this field is doing is forcing geneticists to deal with the immune response. I feel that historically has not been dealt together. The two things need to be integrated. The advantage of the gene therapy is that the protein is produced endogenously. There should be the development of some degree of tolerance with time in the body towards the endogenous continuous production of a protein.Now, will that happen all the time? I still do not know. Again, we need to understand much better what is the integration of the immune system with the response to gene therapy in the ongoing clinical trials.

Nicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfessor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discussed the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025, and is intended for healthcare professionals only. This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Longo will discuss ongoing gene therapies in lysosomal disorders.Nicola Longo MD, PhDI'm going to present to discuss some example of ongoing gene therapy for lysosomal disorder. There are gene therapy in development for both Fabry disease and some of this involve ex vivo gene therapy, many others involve systemic administration with an AAV, Gaucher disease type 1 that affect the periphery, and Gaucher disease type 2, where the replacement should occur within the central nervous system because this condition affects the brain. There is already one approved gene therapy for lysosomal disorder, which is for the early onset metachromatic leukodystrophy. This has been approved both in Europe and now even in the United States, which consists of ex vivo gene therapy with the administration of an extra gene that restore the function of the defective enzyme. Now there are many others that are ongoing for the same indication. There are gene therapy programs for GM1 and GM2 gangliosidosis, and at least one for Krabbe disease. It is important to know that some of these condition are actually included in the recommended uniform screening panel. Basically, we would have access to patients in a timely manner for some of these conditions. Then there are several gene therapy under development for the mucopolysaccharidoses, including MPS-IH, MPS-II, MPS-IIIA and MPS-IV.There are different type of lysosomal disorders, the one caused by mutation, integral membrane protein, not enzyme within the lysosome, but protein that are present on the membrane of the lysosome. This gene therapy that have been tested, it is for cystinosis, that it is caused by a defective lysosomal and for Danon disease, which is caused by a deficiency of an integral membrane part. Finally, one lysosomal disorder, which obviously seems a metabolic condition, but it is really not, is glycogen storage disease type 2 or Pompe disease, in which there is the intralysosomal accumulation of glycogen. There are several ongoing clinical trials to try to correct the problem in this condition.Now, I'm going to discuss some of the most advanced program in the lysosomal storage disorder. This include one for Fabry, which is on an accelerated approval pathway with phase 1 and 2 data, one for Gaucher disease type 1. Obviously, I'm going to discuss the one that has been already approved for metachromatic leukodystrophy. There is one for Hunter syndrome, and the difference of the one for Hunter syndrome, it is an example of the direct administration of gene therapy within the central nervous system.Finally, there is one ongoing for glycogen storage disease type 2 or Pompe disease in adult patients. In gene therapy for metachromatic leukodystrophy, it was the first gene therapy approved for lysosomal disorder in human, and this requires harvesting the CD34 cell from affected patient and then introducing the [inaudible 00:04:32] gene back in this cell, and then placing them back inside the patient again. This has been very effective in patients who were treated early, and obviously, the treatment needs to occur before there is irreversible brain damage in this patient.In the next part, Dr. Roberts and Longo will discuss treatment with gene therapies.

Nicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfessor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discussed the current status of gene therapies in rare neuromuscular disorders in this eight part podcast series. This is derived from the symposium that was presented at World Symposium 2025, in San Diego, California, on February 4th through 7th, 2025, and is intended for healthcare professionals only. This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established, and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Longo will discuss gene replacement therapy in lysosomal disorders.Nicola Longo MD, PhDLet's go back a second to gene therapy. Gene therapy obviously has the potential of answering many of the questions that we still have open in lysosomal disorder because they could restore the activity of the lysosome pretty much in the whole body, or at least in multiple tissues. As you have seen, gene therapy can be done ex vivo where we take cells from the affected patient, we correct the gene, or we put an extra gene that it is functional. Then we put them back by doing a bone marrow transplant, basically creating space for the cells that have been genetically modified to correct the lysosomal defect. The biggest approach this is done usually by lentiviruses that they integrate inside the genome.

Nicola Longo MD, PhD, and Mark Roberts, MDDrs. Longo and Roberts discuss the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at WORLDSymposium 2025 in San Diego, California on February 4th-7th 2025 and is intended for healthcare professionals only.This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses.The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Longo will discuss the current treatment landscape and limitations in lysosomal disorders.Nicola Longo MD, PhDWhat I want to do today, is just place gene replacement therapy within the current landscape of lysosomal storage disorder treatment therapy. Gene therapy obviously has the potential of treating lysosomal disorder to correct the root cause of lysosomal storage disorder. The gene is defective, and what happen is that you can potentially either fix the gene or bypass the lack of the genetic product. But there are already therapies that are existing and are functioning. Obviously, in many cases, the lysosomal disorder is caused by defective production of an enzyme, which is defective.We can either replace the enzyme with enzyme replacement therapy, or provide chaperone for specific mutations that retain the synthesis of the enzyme, that however is not very functional. Another avenue that it is being reported is the utilization of substrate reduction therapy. A substrate accumulates, you prevent the synthesis of the substrate to reduce the accumulation of toxic material. What we know now is that this is not enough to produce many lysosomal disorders. In many cases, the lysosomal disorder result sometime in impairment of intracellular trafficking, and sometime in the function of other organelles.At the end, it results in the activation of the macrophagic system and inflammation. Already we have some therapy acting at this level. The end result of lysosomal storage disorder, there will be cell suffering and cell death, leading to a progression of the disease, and morbidity and mortality. Now, what therapy do we have available already? Obviously, hematopoietic stem cell transplantation has been around for quite some time.It has been the same thing that we do with gene therapy, except that instead of reintroducing the gene of the subject, we place gene of a subject who is not affected of the disease. This therapy has been proven effective in cases of MPS-1 and alpha-mannosidosis. But in many cases this has to be given way before symptoms start to be affected.Enzyme replacement therapy has been around for quite some time, starting with Gaucher disease, and now that it is available for a list of diseases that are there, so it's like Fabry, Gaucher, Pompe, different types of mucopolysaccharidosis, alpha-mannosidosis, acid lipase deficiency, 1 neuronal ceroid lipofuscinosis, and Niemann-Pick type A and B.Obviously the advantage of this therapy, they give back the enzyme that it is defective. But the disadvantage that many time they cannot enter specialized areas such as the brain. There is already the second generation of enzyme replacement therapy that it is available. With this second generation, some of the newer drugs are more effective in terms of cellular uptake, or in terms of having a prolonged half-life and prolonged activity.Then there are pharmacological chaperone therapy, and the one which is FDA approved is migalastat for Fabry disease, under study is ambroxol for Gaucher disease. The disadvantage of this therapy that only a selected number of mutations respond to this therapy.Substrate reduction therapy has been introduced for Gaucher disease many years ago with miglustat, and it was followed by eliglustat. Both of them are effective, and some of them more effective than other, simply because of the fewer side effects of eliglustat as compared to miglustat. But at the same time, eliglustat does not pass the blood brain barrier.Finally, the newer agents that are already administered, N-acetyl-L-leucine and arimoclomol, both approved for Niemann-Pick type C, they act more on the downstream effect of the lysosomal storage disorder, either by stabilizing neuronal cell activity or by reducing the inflammation that is present in the brain.In the next part, Dr. Longo will discuss gene replacement therapy in lysosomal disorders.

Nicola Longo MD, PhD, and Mark Roberts, MDNicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfessor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs.Longo and Roberts discussed the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025 and is intended for healthcare professionals only.This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas.In this part, Dr. Roberts will discuss lessons learned from gene therapy trials.Mark Roberts, MDWhen we think about the challenges of actually doing clinical trials with these gene therapies, there's a huge development stage in terms of picking the right viral vector with the right surface receptor. That's a major piece of work. That can often take years. The preclinical work is obviously very important as indeed is understanding the natural history because it's really not practical to do placebo-controlled trials of gene therapies.In contrast to other studies, when we turn to phase 1 and phase 2, you'll notice that the patient numbers are often quite small. One is having to think carefully about surrogate measurements of response. Especially when in phase 3 studies, we may be thinking about withdrawing the existing, for example, enzyme replacement therapy because we believe the gene therapy will then be effective.That's just a few snapshots of where we've come and there's a lot more work to be done.In the next part, Dr. Longo will discuss the current treatment landscape and limitations in lysosomal disorders.

Nicola Longo MD, PhD, and Mark Roberts, MDNicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfesor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discuss the current status of gene therapies in rare neuromuscular disorders in this 8-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th-7th 2025 and is intended for healthcare professionals only.This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses.The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Roberts will discuss immune responses and other safety concerns related to gene therapies.Mark Roberts, MDUndoubtedly, the immune system is a major issue in these patients. It would be fantastic if we could immunotolerize our patients and indeed prevent the rejection of the therapy. We've talked about the fact that these are viral vectors and of course there may be high seroprevalence of antibodies to these viral vectors, and it's very important in the pre-screening of patients who might be eligible to understand that at the beginning. These of course can have developed over the years and of course can be part of immunological memory and therefore extremely difficult and probably impractical to actually shift.On giving the treatment though as I think we're all aware there is this problem of the innate immunity and potential therefore for acute toxicities and then a learned or adaptive response with cytotoxic T cells and antibodies which may of course become high tighter neutralizing antibodies and potentially antibodies not only against the viral vector, even the functional protein, even the transgene are all theoretical possibilities with time. The capsid, the transgene, and even the protein product can all potentially induce an immunological event. Of course, all of these would lead to both potential patient changes and then a lack of efficacy of the treatment.Indeed, there have been some serious and indeed fatal problems in the gene therapy development program as I think we're all aware. Though many of these are thankfully been overcome. Spinal muscular atrophy has a gene therapy which is licensed, but there were early patients who actually had significant problems. A patient of just 6 months of age who developed kidney failure, two other patients who actually developed liver failure.In Duchenne muscular dystrophy, a very common condition, again there were significant issues and crucially in these patients who all have cardiomyopathy, it was heart failure and cardiac arrest that were big concerns and pulmonary edema and this was seen even with a CRISPR-based technology and is perhaps is best known but has been addressed the excellent myotubular myopathy patients, four patients died and crucially quite a long time after the gene therapy emphasizing the need to monitor these patients extremely carefully and these patients died of cholestatic liver failure albeit that they had a degree of liver dysfunction.That's changed our screening of course of patients, we're now all looking in myotubular patients for liver involvement and Rett syndrome as well. Now these immunoprophylaxis treatment regimes to hopefully try and reduce the immunological reaction against the gene are certainly evolving.This is just a summary of some of the other immunosuppressive regimes used in other disorders, for example, spinal muscular atrophy, but Pompe and MPS as examples of LSDs. Certainly these regimes will continue to evolve and are going to be very important in seeking to make sure that these treatments are effective. It reminds me somewhat of what's happened with enzyme replacement therapy that the use of these immunological strategies in infants has revolutionized the utility of those treatments in early patients.In the next part, Dr. Roberts will discuss lessons learned from gene therapy trials.

Nicola Longo MD, PhD, and Mark Roberts, MD Nicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfesor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discuss the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025 and is intended for healthcare professionals only. This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice.The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Roberts will discuss vectors, different strategies, modes of administration and targets in gene replacement therapies.Mark Roberts, MDNow in the broader sense, gene replacement therapy seeks to actually deliver genetic material directly into the host cell to influence gene expression. In the most simple idea, one of course has a vector, this is most commonly but not exclusively a virus, which can then be given intravenously for example, and can hope to potentially correct the condition within the individual cells using novel transgenes. Suitable candidate conditions for this as examples of genetic conditions are now well understood. And crucially, this applies not only towards some more recessive, but dominant and even accident conditions.Across the piece, one can see for example, mitochondrial problems, spinal muscular atrophy as is well known, X-linked myotubular myopathy, Duchenne muscular dystrophy, a very common condition affecting one in 3000 male individuals, Pompe disease of course, an important focus of the meeting here, but other very common conditions, for example, cystic fibrosis, immunological conditions and perhaps obviously very crucial in early work on gene therapy, hemophilia.Let's now think about the approaches to gene therapy. One can seek to work at the DNA level and gene replacement. In essence, one is trying to put a new transgene through into the nucleus that will ultimately be transcribed and translated and produce the important functional protein that is lost. Gene editing which is a very exciting new technology or CRISPR technology actually seeks to actually modify in vivo the actual mutations that are responsible for the pathogenic production of abnormal proteins and correcting these and actually producing a more normalized protein.But of course there are also RNA approaches where one seeks to actually repair the mRNA transcripts copied from the mutated gene. For example, this may be a novel approach that could be extremely useful in myotonic dystrophy, a multisystem condition. When we talk about the viral vectors, predominantly we're talking about viruses. Those such as adenoviruses and AAV viruses which have the virtue of not integrating into the host genome or at least not in a large amount, and those which deliberately seek to integrate into host genome such as retroviral or lentiviral systems that may be particularly useful for ex vivo systems.There are of course other ways to get genetic payloads into the nucleus, various polymers, nanoparticles and even cell penetrating peptides. Nanoparticles in particular is certainly on the ascendant. That being said, in a recent review of the clinical trials in gene therapy, it was certainly the viral vectors that stood out both in direct gene replacement with lentivirus and AAV, but also actually as delivery systems, for example, for gene editing. An example of what one is seeking to do with AAV, so of course one seeking to remove the native DNA, insert the new transgene directly into the vector and of course keen to make sure that there's a high transmission into the capsid producing a recombinant AAV, which then can be given as a treatment and hopefully produce a therapeutic increase in the functional protein that is deficit in the disorder.In the next part, Dr. Roberts will discuss immune responses and other safety concerns related to gene therapies.

Nicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfessor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discussed the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025, and is intended for healthcare professionals only.This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established, and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses.The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas.In this part, Dr. Roberts will discuss lysosomal disorders and the potential for gene therapies.Mark Roberts, MDI'm going to give an overview of what is gene therapy, emphasizing the current challenges and the development issues and needs that there will be as we try and enable gene therapy for our patients, particularly those with lysosomal storage disorders.I'm going to try and make a case for why lysosomal storage disorders are an extremely good group of conditions for the potential benefits of gene modifying therapies. Firstly, whilst we all recognize that these conditions are inherently individually rare, they're certainly severe. Collectively, with over 70 LSD disorders, 1 in 5,000 may be afflicted by these conditions ultimately in their life and can be detected, for example, by newborn screening programs.Secondly, there's certainly a significant clinical burden with these patients with the current standard of care, so a large unmet need exists. Existing enzyme replacement therapies have undoubtedly changed the natural history of many of these conditions, but there are limitations and often initial benefits and later deteriorations.Unfortunately, for most lysosomal storage disorders, it's only symptomatic treatments and indeed, care that is available for these patients with no specific treatment. Thirdly, these conditions are extremely well-characterized, monogenic singleton and problems of inborn errors of metabolism. We know the functional protein that is deficient in these conditions. Because of that, and knowing that these are critical for lysosomal function, and using preclinical models, we can model the potential benefits of gene therapies very well in a number of systems, including, of course, soon, muscle chip experiments as well.Finally, with these conditions, they may potentially be really useful targets whilst not perhaps curing the condition, at least ameliorating the phenotype, and enabling the addition of other treatments as well, potentially. I've noted, some of these therapies can be directly delivered to certain tissues, so muscle tissue, which is my main interest, but also, crucially, the central nervous system, which is very important when we consider ameliorated phenotypes, for example, treated by enzyme replacement therapy, but where the children who become the adults have significant learning disability as a major component to their problems.In the next part, Dr. Roberts will discuss vectors, different strategies, modes of administration, and targets in gene replacement therapies.

ChairProfessor Yoshikatsu EtoAdvanced Clinical Research Center, Southern Tohoku Research Center for Neuroscience, Tokyo, JapanSpeakersDr Nicole Muschol International Center for Lysosomal Disorders (ICLD), University Medical Center, Hamburg-Eppendorf, GermanyProfessor Patrício AguiarInborn Errors of Metabolism Reference Center, Unidade Local de Saúde de Santa Maria / Faculty of Medicine, Lisbon University, PortugalDr Robert HopkinCincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USAProfessor Yoshikatsu EtoWelcome to the Chiesi symposium. The title of this symposium, Catching the Clues, Changing the Cause of Lysosomal Storage Disease: Illuminating Complex Pathway of Rare Disease with Fabry Disease, Alpha-Mannosidosis, in Focus.This is a disclaimer: Following discussion does not focus on or depict any specific products manufactured by any pharmaceutical company. Patient cases are for medical discussion only and reflect the faculty own experience. They represent a typical clinical scenario. This presentation in part and whole may not be reproduced and not copy and not recording.I'm Dr. Eto from Tokyo, Japan, and the three distinguished speakers: Dr. Nicole Muschol from Germany, Eppendorf University. Professor Aguiar, the Portuguese, The Inborn Errors of Metabolism Reference Center, and also Professor Robert Hopkin, Cincinnati Children's Hospital, United States.The purpose of this symposium: Explore the patient journey across the LSD continuum, focusing on the unmet needs and diagnosis, and treatment initiation, and long-term management, and utilize case-based discussion focused on Alpha-mannosidosis, Fabry disease to highlight disease-specific challenges. Access where challenge persist in patient journey, and where tailored intervention can improve outcomes.Introduction of LSD patient journey with a spotlight on Fabry disease, Alpha-mannosidosis. Challenge to the diagnosis and then treatment and monitoring. Common LSD challenges over the patient journey, as shown here, and at least more than 70 different lysosomal diseases known. Incidence is about 1:5,000-1:8,000 in newborn. In the literature, much higher incidence.Multi-organ manifestation in many organ involved, and clinical heterogeneity are very complicated. The new screen method has been established already. Identify patient presymptomatically. That important by the newborn screening, something like that, early treatment essential. After the diagnosis treatment start, early and the presymptomatic treatment initiation, and usually delayed diagnosis, delayed treatment. Perceived burden of treatment may delay treatment start in patient milder form. Milder form is very difficult in the many cases, and particularly for Fabry disease also.After the treatment start and then monitoring, as you know, we discussed about the monitoring rely on the combination of clinical assessment, laboratory test, biomarkers, and imaging, and several other factors. Biomarkers and ADA drug assay lack standardization. Actually, the Alpha, and Beta, or [inaudible 00:03:19] Fabry disease, different ADA-titled measurement. Also, the patient experience between clinical visit, ERT infusion is under-reported.We discuss today two topics, two disease. Alpha-mannosidosis is very rare. In Japan, only few cases, and caused by the deficiency of Alpha-mannosidase, an accumulation of mannose-rich oligosaccharides and inheritance of autosomal-recessive. Age of onset is a very early period and younger period, adult period. Incidence approximately is very rare, 1:500,000.There are diseases we don't know exactly. If you have a treatment, maybe your incidence is much increased, and severe or attenuated [inaudible 00:04:09]. Alpha-mannosidosis is still a new disorder, and must differentiate from Mucopolysaccharidosis.On the other hand, the Fabry disease I think is very common. There are many discussion already in the past 20 years. Deficiency of a-Gal A, accumulation of Gb3⁵­­ or Lyso-Gb3, many other glycoprotein, which a terminal of a-Gal A, and X-chromosome. This is very important X-chromosomal inheritance. In case of this, and usually, female does not affect, but in case of Fabry, more of female also involved.First symptom, imagine at any age. Then incidence about 1:40,000-1:60,000. But depending on the country, as you know, classical form, about 1:40,000. Recently, after the newborn screening, late onset, very high incidence. About 90% of it—actually, we carried out a newborn screening in Japan—90% are late onset. But the clinical variety, so many clinical varieties, so incidents here, 1:3,000-1:4,000, something like that. Now, using the Alpha-mannosidosis and Fabry disease as an illustrative example, we will explore these disorders.

This accredited continuing education program is supported by an educational grant from Sanofi. Credit for the program can be obtained by visiting https://checkrare.com/learning/p-consider-rare-suspecting-and-diagnosing-cidp/ . This program, led by Jeffrey Allen, MD, Professor of Neurology at the University of Minnesota provides an overview on the diagnostic delays that often occur in patients with CIDP as well as best practices to suspect and diagnose this rare condition more efficiently. This activity has been designed to meet the educational needs of physicians specializing in family medicine, pediatrics, and neurology. Other members of the care team may also participate.Learning ObjectivesAfter participating in the activity, learners should be better able to:Describe the early symptoms of CIDP.List best practices which can be used to diagnose CIDP more efficiently.Faculty Jeffrey Allen, MDProfessor of NeurologyDepartment of NeurologyDivision of Neuromuscular MedicineUniversity of MinnesotaMinneapolis, MNDisclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Faculty Educator/PlannerDr. Scott discloses Consultant/Educational talks: Annexon, Alexion, Amgen, CSL Behring, Takeda,BioCryst, Grifols, Argenx, Sanofi, Immunovant, ImmunoAbs, Octapharma, Alnylam, AstraZeneca, Dianthus, Johnson & Johnson, Laboratoire Français du Fractionnement et des Biotechnologies, Nuvig, Akcea Therapeutics, ImmunoPharma,Pfizer.Community Faculty/Patient (Christine Eleeson): No relevant financial relationships with any ineligible companies.Other Planners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information.The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.There are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre-and post-program assessments. Your certificate will be emailed to you within 30 days.PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

Ozlem Goker-Alpan, MD, Founder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) and Raphael Schiffmann, MD, of the Texas Christian University, discuss best practices to identify and treat neurologic problems associated with lysosomal disorders.This continuing education activity is provided through collaboration between the Lysosomal and Rare Disorders Research and Treatment Center (LDRTC), CheckRare CE, and AffinityCE. This activity provides continuing education credit for physicians, physician assistants, nurses, nurse practitioners, and genetic counselors. A statement of participation is available to other attendees. To complete the program and obtain credit, visit https://checkrare.com/learning/p-lysosomal-disorders-and-the-brain/ Support for this educational activity provided by Takeda and Ultragenyx.Learning ObjectivesAfter participating in the activity, learners should be better able to:Describe the role of the neurologist in the team approach to careList best practices to assess neurologic and cognitive involvement  in persons with LDsCite best practices to assess developmental delay and regression in pediatric patients with suspected LDsDescribe the latest clinical research to improve central outcomes in persons with LDs and central nervous system involvementFacultyOzlem Goker-Alpan, MD, Founder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC), Fairfax, VA Raphael Schiffmann, MDTexas Christian University,Fort Worth, TXDisclosuresAffinityCE staff, LDRTC staff, planners, and reviewers, have no relevant financial relationships with ineligible companies to disclose. Faculty disclosures, listed below, will also be disclosed at the beginning of the Program.Ozlem Goker-Alpan MDDr. Goker-Alpan is on the Advisory Board/Consultant for Chiesi, Takeda, Sanofi, Prevail/Lilly, Sparks Therapeutics, Uniqure, Exegenesis, Astellas, Freeline, Team Sanfilippo. She receives grants/research support from Chiesi, Sanofi, Takeda, Prevail/Lilly, Spark Therapeutics, Amicus, Freeline, Sangamo, Cyclo, Odorsia, $DMT, Homology, Protaliz. She is on the speaker bureau for Sanofi, Takeda, Amicus, Chiesi.Raphael Schiffman, MDDr. Schiffmann is consultant for Amicus Therapeutics, Protalix Biotherapeutics, Chiesi Farmaceutici and 4D Molecular TherapeuticsMitigation of Relevant Financial RelationshipsAffinityCE adheres to the ACCME's Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of the activity. Conflicts of interest for presenting faculty with relevant financial interests were resolved through peer review of content by a non-conflicted reviewer. PhysiciansThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Physician AssistantsThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Physician Assistants should claim only the credit commensurate with the extent of their participation in the activity.NursesContinuing Nursing Education is provided for this program through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation (ANCC). This activity provides a maximum of 1 hours of continuing nursing education credit.Nurse PractitionersThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Nurse practitioners should claim only the credit commensurate with the extent of their participation in the activity.Genetic CounselorsCategory 2 CEUThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credit™. Genetic counselors should claim only the credit commensurate with the extent of their participation in the activity.CME InquiriesFor all CME policy-related inquiries, please contact us at mailto:ce@affinityced.comSend customer support requests to mailto:cds_support+ldrtc@affinityced.comCopyright© 2025. This CME-certified activity is held as copyrighted © by Lysosomal and Rare Disorders Research and Treatment Center (LDRTC) and AffinityCE. Through this notice, Lysosomal and Rare Disorders Research and Treatment Center (LDRTC) and AffinityCE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

This program, led by Christiaan Scott, MD, Professor of Pediatric Rheumatology at the University of Ottawa and Raphaella Stander, MBCHB, Pediatrician at Atlantic Children's Practice, focused  on three case studies to provide physicians with education on best practices to: 1) suspect and diagnose FOP, 2) monitor and manage younger children with FOP, and 3) monitor and manage older children and adults with FOP. This accredited CME program provides healthcare professional with timely and practical education on fibrodysplasia ossificans progressiva (FOP). It is supported by an educational grant from Ipsen Biopharmaceuticals.To obtain CME credit, visit https://checkrare.com/learning/p-case-studies-in-diagnosing-and-managing-fop/ Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in pediatrics, rheumatology, genetics, family medicine, and orthopedics. Other members of the care team may also participate.Learning ObjectivesAfter participating in the activity, learners should be better able to:Apply best practices for suspecting and diagnosing FOP.List best practices for managing young children with FOP.Identify best practices to manage older children and adults with FOP.Christiaan Scott, Professor of Medicine, University of OttawaRaphaella Stander, MBCHB, Pediatrician, Atlantic Children's PracticeDisclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Faculty Educator/PlannerDr. Scott discloses the following relevant financial relationships with ineligible companies:Grant/Research Support: Regeneron*, Incyte*, Janssen*, Roche*; Speaker's Bureau:  Ipsen*, Regeneron*, Springer*, Jannsen**Relationships have endedDr. Stander has no relevant financial relationships with ineligible companies.Other Planners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information.The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.There are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you within 30 days.PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

This accredited CME program highlights the latest clinical research about immune thrombocytopenia (ITP), a rare thrombotic disorder. Led by Shruti Chaturvedi, MD, this program provides a summary of clinically relevant data presented at the International Society of Thrombosis and Haemostatis Congress (ISTH 2025) that can enhance the care of patients with ITP. This program is supported by an educational grant from Sanofi.To receive CME credit, go to https://checkrare.com/learning/p-isth2025-module2-immune-thrombocytopenia-clinical-research-highlights/Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in ITP. Other members of the care team may also participate.Learning ObjectivesAfter participating in the activity, learners should be better able to:Describe the latest research being presented to better manage individuals with ITP and its clinical relevance.FacultyShruti Chaturvedi, MDAssistant Professor of Medicine,Johns Hopkins Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated. Disclosure of relevant financial relationships are as follows:Faculty Educator/PlannerDr. Chaturvedi discloses the following relevant financial relationships with ineligible companies:Scientific Advisory Board/Consultant: Sanofi, Takeda, Sobi, argenx, Star Pharma, RallyBio, Novartis, AlexionGrant/Research Support: Sanofi, Sobi, argenx Other Planners for this activity have no relevant financial relationships with any ineligible companies. This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation. There are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you within 30 days. PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

The accredited CME program highlights the latest clinical research about iTTP, a rare thrombotic disorder. Led by Shruti Chaturvedi, MD, this activity provides a summary of clinically relevant data presented at the International Society of Thrombosis and Haemostatis Congress (ISTH 2025) that can enhance the care of patients with iTTP. This program is supported by an educational grant from Sanofi.To receive CME credit, go to https://checkrare.com/learning/p-isth2025-module3-immune-thrombotic-thrombocytopenic-purpura-ittp-clinical-research-highlights/Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in iTTP. Other members of the care team may also participate.Learning ObjectivesAfter participating in the activity, learners should be better able to:Describe the latest research being presented to better manage individuals with iTTP and its clinical relevance. Shruti Chaturvedi, MDAssistant Professor of MedicineJohns Hopkins Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated. Disclosure of relevant financial relationships are as follows:Faculty Educator/PlannerDr. Chaturvedi discloses the following relevant financial relationships with ineligible companies:Scientific Advisory Board/Consultant: Sanofi, Takeda, Sobi, argenx, Star Pharma, RallyBio, Novartis, AlexionGrant/Research Support: Sanofi, Sobi, argenx Other Planners for this activity have no relevant financial relationships with any ineligible companies. This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information. Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation. There are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you within 30 days. PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

The accredited CME program highlights the latest clinical research about hemophilia, a rare, genetic bleeding disorder. Led by Dr. Steven Pipe, MD, this activity provides a summary of clinically relevant data presented at the International Society of Thrombosis and Haemostatis Congress (ISTH 2025) that can enhance the care of patients with hemophilia. This program is supported by an educational grant from Sanofi.To receive CME credit, visit https://checkrare.com/learning/p-isth2025-module1-hemophilia-clinical-research-highlights/Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in hemophilia. Other members of the care team may also participate.Learning ObjectivesAfter participating in the activity, learners should be better able to:Describe the latest research being presented to better manage individuals with hemophilia and its clinical relevance.Steven Pipe, MDProfessor of Medicine,University of Michigan Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated. Disclosure of relevant financial relationships are as follows:Faculty Educator/PlannerDr. Pipe discloses the following relevant financial relationships with ineligible companies:Consultant: Bayer, BioMarin, CSL Behring, Hema Biologics, Inovio, LFB, Metagenomi, Novo Nordisk, Pfizer, Poseida Therapeutics, Roche/Genentech, Sanofi, Takeda, Spark TherapeuticsScientific Advisory Committee: GeneVentiv, Equilibra BioscienceGrant/Research Support: Siemens, YewSaving Other Planners for this activity have no relevant financial relationships with any ineligible companies. This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information. Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation. ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

This program is supported by an educational grant from UCB, Inc. This accredited CME program highlights the latest clinical research about myasthenia gravis, a rare, autoimmune disease that targets the neuromuscular junction.  This program, led by Dr. James Howard Jr, provides a summary of clinically relevant data presented at the American Academy of Neurology Annual Meeting (AAN 2025) held in San Diego, CA that can enhance the care of patients with myasthenia gravis.  To obtain CME credit for this program, visit https://checkrare.com/learning/p-myasthenia-gravis-clinical-research-highlights-aan-2025/Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in neurology, ophthalmology, rheumatology, and family practice. Other members of the care team may also participate.Learning ObjectivesAfter participating in the activity, learners should be better able to:Describe the latest research being presented to better manage individuals with myasthenia gravis and its clinical relevance.FACULTY James F. Howard Jr, MD, FAANProfessor of NeurologyUniversity of North Carolina at Chapel HillDisclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Faculty Educator/PlannerDr. Howard discloses the following relevant financial relationships with ineligible companies:Advisory Board/Consultant: Alexion AstraZeneca Rare Disease, Amgen, argenx, Biohaven Ltd, Cartesian Therapeutics, CoreEvitas, Curie.bio, Hansa Biopharma, H. Lundbeck A/S, Merck EMD Serono, NMD Pharma, Novartis Pharma, Regeneron Pharmaceuticals, Sanofi US, Seismic Therapeutics, TG Therapeutics, Toleranzia AB, and UCB PharmaGrant/Research Support: Ad Scientiam, Alexion AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, NMD Pharma, and UCB PharmaOther Relationships: non-financial support (eg travel) Alexion AstraZeneca Rare Disease, argenx, Biohaven Ltd, Cartesian Therapeutics, Toleranzia AB, and UCB Pharma.Other Planners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information.The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.CREDIT Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.There are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you within 30 days.PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

Warner Carr, MD, Allergist and Immunologist at the Allergy and Asthma Associates of Southern California, discusses the mastocytosis control test and its implications for physicians.

Ozlem Goker-Alpan, MD, Founder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC) and Ravi Kamath, MD, PhD, of Fairfax Radiological Consultants & Inova Health System and University of Virginia School of Medicine Fairfax, Virginia, USA discuss best practices to identify and treat bone problems associated with lysosomal disorders.This continuing education activity is provided through collaboration between the Lysosomal and Rare Disorders Research and Treatment Center (LDRTC), CheckRare CE, and AffinityCE. This activity provides continuing education credit for physicians, physician assistants, nurses, nurse practitioners, and genetic counselors. A statement of participation is available to other attendees.This educational program is supported by an educational grant from Takeda and Ultragenyx.To obtain credit, visit https://checkrare.com/learning/p-skeletal-involvement-in-lysosomal-disorders/quizzes/evaluation-skeletal-involvement-in-lysosomal-disorders/ FacultyOzlem Goker-Alpan, MD, Founder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC), Fairfax, VA Ravi Kamath, MD, PhD,Fairfax Radiological Consultants & Inova Health System and the University of Virginia School of Medicine, Fairfax, VirginiaDisclosuresAffinityCE staff, LDRTC staff, CheckRare staff, planners, and reviewers, have no relevant financial interests to disclose. All faculty disclosures are listed below and are included in the beginning of each presentation.Dr. Goker-Alpan is on the Advisory Board/Consultant for Chiesi, Takeda, Sanofi, Prevail/Lilly, Sparks Therapeutics, Uniqure, Exegenesis, Astellas, Freeline, Team Sanfilippo. She receives grants/research support from Chiesi, Sanofi, Takeda, Prevail/Lilly, Spark Therapeutics, Amicus, Freeline, Sangamo, Cyclo, Odorsia, DMT, Homology, Protaliz. She is on the speaker bureau for Sanofi, Takeda, Amicus, ChiesiDr. Kamath is on the Advisory Board for Spur Therapeutics and Intrinsic Therapeutics. He is also a consultant for Sanofi, Shire and Takeda.  Mitigation of Relevant Financial RelationshipsAffinityCE adheres to the ACCME's Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of the activity. A non-conflicted reviewer resolved conflicts of interest for presenting faculty with relevant financial interests through peer review of content.Learning ObjectivesDescribe the role of the orthopedic surgeon in the team approach to careDescribe best practices to monitor bone abnormalities in persons with LDsDescribe best practices to treat bone abnormalities in persons with LDsDescribe research trends in bone abnormalities in persons with LDsPhysiciansThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Physician AssistantsThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Physician Assistants should claim only the credit commensurate with the extent of their participation in the activity.NursesContinuing Nursing Education is provided for this program through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation (ANCC). This activity provides a maximum of 1 hours of continuing nursing education credit. Nurse PractitionersThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credits™. Nurse practitioners should claim only the credit commensurate with the extent of their participation in the activity.Genetic CounselorsCategory 2 CEUThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1 AMA PRA Category 1 Credit™. Genetic counselors should claim only the credit commensurate with the extent of their participation in the activity.Other ProfessionalsAll other health care professionals completing this continuing education activity will be issued a statement of participation indicating the number of hours of continuing education credit. This may be used for professional education CE credit. Please consult your accrediting organization or licensing board for their acceptance of this CE activity.Commercial Support Support for this educational activity was provided by Takeda and Ultragenyx. Participation CostsThere is no cost to participate in this activity.CME InquiriesFor all CME policy-related inquiries, please contact us at ce@affinityced.com.Send customer support requests to cds_support+ldrtc@affinityced.com.

This program is supported by educational grants from Amicus Therapeutics, Inc. and Chiesi USA Inc.Fabry disease is an inherited lysosomal storage disease caused by mutations in the GLA gene, disrupting the function of the enzyme, α-galactosidase. This results in the accumulation of globotriaosylceramide (GL-3) and its deacylated form, globotriaosylsphingosine (lyso-GL-3), leading to progressive disruption of multiple organ systems. There are currently three treatment options available for Fabry disease, including two enzyme replacement therapies, agalsidase beta and pegunigalsidase alfa, and a chaperone therapy, migalastat. There are also other treatments in development (e.g., gene therapy, other enzyme replacement therapies) and some that are available in other countries (e.g., agalsidase alfa). Due to the small patient population and variability in Fabry disease severity, it is challenging to develop properly powered, placebo-controlled clinical trials. As such, data shared at conferences like WORLDSymposium 2025 are crucial for guiding best practices in this disease area. This program, led by Dr. Eric Wallace, provides a summary of clinically relevant data presented at WORLDSymposium 2025 that can enhance the care of patients with Fabry disease.  Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in neurology, nephrology, cardiology, gastroenterology, ophthalmology, and dermatology. Other members of the care team may also participate.Learning ObjectivesAfter participating in the activity, learners should be better able to: Describe the latest research being presented to better manage individuals with Fabry disease and its clinical relevance.Eric Wallace, MDProfessor of MedicineDepartment of NephrologyUniversity of Alabama Medical SchoolDisclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Faculty Educator/PlannerDr. Wallace discloses the following relevant financial relationships with ineligible companies:Advisory Board Consultant: Sanofi-Genzyme, Chiesi, Kyowa Kirin, Sangamo, NateraGrant/Research Support: Sanofi-Genzyme, Chiesi, Uniqure, Idorsia, Amicus Other Planners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information.The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.There are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you within 30 days.Hardware/Software RequirementsWindows Requirements: • Operating system: Windows XP Service Pack 2 or later • Browser: Internet Explorer 7 or later, Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionMacintosh Requirements: • Operating system: Mac OS X v10.3 or later • Browser: Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionPrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by abnormal bone development. Most babies with FOP appear normal and healthy at birth with one exception—the appearance of deformed big toes. Unfortunately, this common deformity can be attributed to other causes. This can result in a delay of years before a person is diagnosed with FOP properly. This educational webinar, hosted by Ellen Elias, MD, Professor, Pediatrics and Genetics, University of Colorado School of Medicine, and Christiaan Scott, MD, Professor of Medicine at the University of Ottawa, examines best practices to suspect and diagnose this ultra-rare condition.This educational program is made possible by an unrestricted grant from the International Fibrodysplasia ossificans progressiva Association (IFOPA).To see the video, please visit https://checkrare.com/suspecting-and-diagnosing-fibrodysplasia-ossificans-progressiva-fop/ 

This educational program, hosted by Patrick McKiernan, MD, Pediatric Hepatologist at Birmingham Children's Hospital NHS Foundation Trust and Nadia Ovchinsky, MD, Professor of Medicine at NYU Grossman School of Medicine discuss the recently published guidance on best practices to diagnose, treat, and monitor patients with PFIC. It also explains why the new guidance recommends the early use of IBAT inhibitors in patients suspected of having progressive familial intrahepatic cholestasis (PFIC).PFIC encompasses a spectrum of autosomal recessive disorders characterized by impaired bile flow (cholestasis) due to defects in biliary epithelial transporters. These rare genetic conditions typically manifest in infancy or early childhood, leading to severe liver dysfunction and potentially life-threatening complications if left untreated. Common early symptoms observed in children with PFIC are jaundice, pruritus, elevated serum bile acid (SBA) values, malabsorption, and failure to thrive. PFIC can be a debilitating condition that significantly impacts the quality of life and can result in end-stage liver disease. As such, early detection and effective intervention are imperative for the prevention of disease progression. Unfortunately, there are no relevant guidelines based on newly published research to help healthcare providers manage patients with PFIC. However, a recent opinion paper by leading experts in the management of PFIC provides evidence-based guidance on this subject and was recently published in JHEP Reports. This educational program is made possible by an unrestricted grant from Ipsen.

This CME program provides information on best practices to manage children with lysosomal disorders who have been identified by newborn screening. WIth the wide range of symptoms and severities that present for these rare conditions, it is not always certain when the best time to start treatment is in these patients.Continuing Education InformationThis continuing education activity is provided by AffinityCE and the Lysosomal and Rare Disorders Research and Treatment Center (LDRTC). This activity provides continuing education credit for physicians. A statement of participation is available to other attendees.To obtain credit, visit https://checkrare.com/learning/p-transforming-clinical-outcomes-with-early-treatment-of-lysosomal-disorders/ Faculty and DisclosuresAffinityCE staff, LDRTC staff, planners, and reviewers, have no relevant financial relationships with ineligible companies to disclose. Faculty disclosures, listed below, will also be disclosed at the beginning of the Program.Ozlem Goker-Alpan MDFounder and CMO, Lysosomal & Rare Disorders Research & Treatment CentersDr. Goker-Alpan is on the Advisory Board/Consultant for Chiesi, Takeda, Sanofi, Prevail/Lilly, Sparks Therapeutics, Uniqure, Exegenesis, Astellas, Freeline, Team Sanfilippo. She receives grants/research support from Chiesi, Sanofi, Takeda, Prevail/Lilly, Spark Therapeutics, Amicus, Freeline, Sangamo, Cyclo, Odorsia, DMT, Homology, Protaliz. She is on the speaker bureau for Sanofi, Takeda, Amicus, ChiesiDavid F. Kronn MDAssociate Professor of Pathology and Pediatrics                                                New York Medical CollegeDr. Kronn is on the Advisory Board for Sanofi. He is also on the speaker bureau for Sanofi. He receives research funding from Sanofi.Uma Ramaswami FRCPCH, MDRoyal Free London Hospitals & Genetics and Genomic Medicine, University College LondonDr. Ramaswami is on the Advisory Board for Amicus, Chiesi, Sanofi and Takeda. She receives research grants from Chiesi and Intabio.Liz Jalazo MDAssistant Professor of Pediatrics and GeneticsUniversity of North Carolina at Chapel HillDr. Jalazo is on the Advisory Board for Sanofi and Ionis. Lindsay Torrice MSN, CPNP-PC MDAssistant Professor of PediatricsUniversity of North Carolina at Chapel HillMs. Torrice has no financial relationships to disclose.Mitigation of Relevant Financial RelationshipsAffinityCE adheres to the ACCME's Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible companies. All relevant financial relationships for faculty were mitigated by the peer review of content by non-conflicted reviewers before the commencement of the activity.Learning ObjectivesAt the end of this activity, participants should be able to:•     Cite the importance of early diagnosis and treatment of lysosomal storage disorders•     List the guidelines for the early treatment of LDs and enhanced integration of newborn screening programs•     Identify key research gaps and priorities and strengthen collaboration among researchers and healthcare professionals•     List the educational resources and support programs for familiesPhysiciansThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Other ProfessionalsAll other healthcare professionals completing this continuing education activity will be issued a statement of participation indicating the number of hours of continuing education credit. This may be used for professional education CE credit. Please consult your accrediting organization or licensing board for their acceptance of this CE activity.Commercial SupportThis activity was supported by educational grants from Takeda, Sanofi, and Chiesi.Participation CostsThere is no cost to participate in this activity. CME InquiriesFor all CME policy-related inquiries, please contact us at ce@affinityced.com.Send customer support requests to cds_support+ldrtc@affinityced.com.

This CME program, hosted by Jean Elwing, MD, of the University of Cincinnati College of Medicine provides an overview of the latest clinical research about PAH presented at CHEST 2024.PAH is a rare, progressive disorder characterized by high blood pressure in the pulmonary arteries. Symptoms of PAH include shortness of breath (dyspnea) especially during exercise, chest pain, and fainting episodes. The progressive nature of this disease means that an individual may experience only mild symptoms at first, but will eventually require treatment and medical care to maintain a reasonable quality of life. There are numerous treatment options and options in development for persons with PAH and it is imperative clinicians who manage these patients stay up-to-date on the latest clinical research. Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in pulmonology, cardiology, rheumatology, and radiology. Other members of the care team may also participate.Learning ObjectivesDescribe the latest research being presented to better manage people with PAH and its clinical relevance.CME CreditTo obtain credit, visit https://checkrare.com/learning/p-pah-clinical-research-highlights-chest-2024/Faculty/ DisclosureAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Dr. Elwing discloses the following relevant financial relationships with ineligible companies:Advisory Board Consultant: United Therapeutics, Aerovate Therapeutics, Gossamer Bio, Liquidia, Merck, Janssen/Actelion/Johnson & Johnson, Lung LLC, PulmovantGrant/Research Support: United Therapeutics, Gossamer Bio, Bayer, Acceleron/Merck, Altavant Sciences, Aerovate Therapeutics, Pharmosa Biopharm/Liquidia, Actelion/Janssen/Johnson & Johnson, Lung LLC, PulmovantSpeaking Honorarium: United TherapeuticsPlanners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information.The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically and draw conclusions only after careful consideration of all available scientific information.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactPlease contact: CEServices@academycme.org for any comments or questions.;Copyright © 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

Hereditary angioedema (HAE) is a rare condition often due to reduced levels C1-inhibitor, which is a protein involved in various physiological processes in plasma, most notably with the complement system. C1-inhibitor also binds and inhibits plasma kallikrein and factor XIa, thereby affecting bradykinin production. It is believed that the disruptions of these processes cause fluid to leak from the blood to connective tissue, leading to HAE attacks. Owing to its rarity, HAE is often poorly recognized, leading to misdiagnoses and significant diagnostic delays. Being aware of the early signs and symptoms of this condition can lead to faster diagnosis and the use of effective therapies.This program is supported by independent medical education grants from Takeda. To earn CME credit please visit https://checkrare.com/learning/p-consider-rare-suspecting-and-diagnosing-hereditary-angioedema/lessons/consider-rare-suspecting-and-diagnosing-hereditary-angioedema-module/  Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in primary care, pediatrics, emergency care, otolaryngology, gastroenterology, and dermatology .Other members of the care team may also participate.Learning ObjectivesAfter participating in the activity, learners should be better able to:- Describe the early symptoms of HAE and its clinical relevance.- Apply best practices to diagnose HAE more efficiently to reduce diagnostic delays. Faculty Jonathan A Bernstein, MDProfessor of MedicineUniversity of Cincinnati Department of Internal MedicineDivision of Immunology, Allergy SectionPartner Advanced Allergy Services, LLCPartner Bernstein Clinical Research Center Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Dr. Bernstein discloses the following relevant financial relationships with ineligible companies:Advisory Board Consultant: Takeda/Shire, CSL Behring, KalVista, Pharming, Biocryst, Ionis, Intellia, Pharvaris, Astria and BiomarinGrant/Research Support: Takeda/Shire, CSL Behring, KalVista, Pharming, Biocryst, Ionis, Intellia, Pharvaris, Astria and BiomariSpeaker's Bureau: PharmingPlanners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information.The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.There are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you within 30 days.ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2025. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

This educational program is made possible by an unrestricted grant from Takeda Pharmaceuticals.Hereditary angioedema (HAE) is a rare genetic disease that results in immunologic attacks that can be life-threatening. HAE is the result of reduced levels of C1-inhibitor, a protein involved in various physiological processes in plasma, most notably with the complement system. C1-inhibitor also binds and inhibits plasma kallikrein and factor XIa, thereby affecting bradykinin production. It is believed that the disruptions of these processes lead to fluid leaking from the blood to connective tissue which leads to HAE attacks. It is these HAE attacks that tend to put persons in the emergency department or unable to attend work or school.Numerous therapies are now available for patients with HAE to both treat acute attacks and prevent attacks via prophylactic treatment.With so many treatment options now available, is it disheartening to learn that not all patients with HAE are receiving equal care or access to care. Patients with HAE living in rural areas as patients from underrepresented racial or ethnic backgrounds are not provided the same level of care as patients, especially Caucasian patients,  living in more affluent areas. This panel discussion by three clinical research leaders in HAE, Drs. Aleena Banerji, Timothy Craig, and Marc Riedl, provide an overview of the discrepancies in care observed in certain patient populations, as well as a discussion on best practices to reduce those inequalities moving forward.To view this program in video format, go to https://checkrare.com/improving-health-equity-in-hereditary-angioedema-hae-a-panel-discussion/

João GonçalvesFaculty of PharmacyUniversity of LisbonLisbon, PortugalPaolo CalicetiDepartment of Pharmaceutical and Pharmacological SciencesUniversity of PadovaPadova, ItalyWhat Is PEGylation and Why Is It Important?We will begin by examining the clinical uses of therapeutic proteins, and their applications in healthcare. Next, we will discuss the inherent limitations of therapeutic proteins, including challenges such as pharmacokinetic (PK) profiles, protein aggregation during storage, and potential immune responses. The session will then delve into the process of PEGylation, where polyethylene glycol (PEG) is conjugated to functional amino acid groups on the protein surface. This modification may enhance the properties of therapeutic proteins, offering advantages in stability, half-life, and immunogenicity.Biopharmaceutical and Immunological Properties of PEGylated ProteinsWe will explore the biopharmaceutical and immunological properties of PEGylated proteins, focusing on how their unique structure and composition impact their function. We will discuss how each PEGylated protein has distinct properties based on PEG architecture, molecular weight and degree of conjugation that cannot be generalized across different pegylated molecules, highlighting the variability in pharmacokinetic (PK) characteristics such as half-life, absorption, distribution, and elimination. These factors can significantly influence clinical outcomes, including dosing intervals and overall therapeutic effectiveness. We will also address the potential clinical advantages and limitations of PEGylation, with real-world examples to illustrate how these proteins are used in practice.Immunogenicity Considerations of PEGylated ProteinsWe will explore the immunogenicity of PEGylated proteins, examining both the potential benefits and risks associated with PEG modification. While PEGylation can trigger immune responses against PEG itself or the PEGylated protein, it can also help mask epitopes and reduce anti-drug antibodies formation. Drug- and patient-related factors that influence immunogenicity risk will also be covered, along with the prevalence and impact of pre-existing anti-drug antibodies (ADAs).We will discuss the potential clinical consequences of immune reactions to PEG or PEGylated proteins, and how the risk of such responses can vary depending on the unique properties of each PEGylated protein. The session will also address strategies to mitigate anti-PEG immunogenicity, as well as approaches for monitoring immunogenicity across different stages of drug development—from preclinical studies to post-marketing surveillance. Additionally, we will explore tools that may help predict therapeutic responses to PEGylated proteins, touching on potential areas for future research.Discussion and ConclusionBy the end of the session, participants will gain a comprehensive understanding of:How PEGylation represents a major technological advancement in the development and optimization of therapeutic proteins.How PEGylation affects both the biopharmaceutical properties and clinical applications of therapeutic proteinsImmunogenicity in the context of PEGylated proteins and the strategies used to manage and predict immune responses.The role of PEGylation in therapeutic outcomes and the future opportunities for innovation in this field.

This 30-minute CME-accredited program, hosted by John Kuruvilla, MD, discusses best practices for talking to patients with hematologic malignancies about possibly participating in clinical trials.Jointly Provided by American Academy of CME and CheckRare CE.Support for this accredited continuing education activity has been made possible through educational grant from Merck.Estimated time to complete: 0.5 hours Start date: November 30, 2024End date: November 30, 2025  Activity FacultyJohn Kuruvilla, MDHematologist / Clinical InvestigatorPrincess Margaret Cancer CentreProfessor of MedicineUniversity of Toronto Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in hematology-oncology. Other healthcare providers, including NPs and PAs, may also participate. Learning ObjectivesAfter participating in the activity, learners should be better able to- Describe the importance of clinical trials in furthering the science of hematologic malignancies treatment.- Describe and utilize best practices for engaging patients in shared decision making regarding clinical trial participation. Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation. Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows: Faculty Educator/PlannerDr. Kuruvilla discloses the following relevant financial relationships with ineligible companies:Honoraria: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Beigene, Genmab, Gilead Sciences, GlaxoSmithKline, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle GeneticsConsultant: AbbVie, Bristol Myers Squibb, Gilead Sciences/Kite, Merck, Roche, Seattle GeneticsGrant/Research Support: AstraZeneca, Kite, Merck, Novartis, RocheData Safety Monitoring Board: KaryopharmPlanners for this activity have no relevant financial relationships with any ineligible companies. This activity will not review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information. Method of ParticipationThere are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please go to https://checkrare.com/learning/p-hematologic-malignancies-and-clinical-trial-participation-a-shared-decision-making-approach/   PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.org               

Jointly Provided by American Academy of CME Inc and CheckRare CE Inc.Support for this accredited continuing education activity has been made possible through an educational grant from argenx US Inc. and UCB.Estimated time to complete: 0.50 hoursStart date: November 7, 2024End date: November 6, 2025This half-hour CME-accredited program, hosted by Richard J. Nowak, MD, MS, explains the role of  neonatal fragment crystallizable receptor (FcRn) in myasthenia gravis (MG) and how treatments that target FcRn are being used to manage patients with MG.To obtain credit, visit https://checkrare.com/learning/p-fcrn-and-myasthenia-gravis/ Activity FacultyRichard J. Nowak, MD, MSDirector, Program in Clinical & Translational Neuromuscular Research (CTNR) Director, Yale Myasthenia Gravis Clinic Associate Professor of Neurology Division of Neuromuscular MedicineDepartment of Neurology Yale School of Medicine New Haven, CTTarget AudienceThis activity has been designed to meet the educational needs of physicians specializing in neurology and ophthalmology who may be involved in the diagnosis and care of individuals with MG. Other healthcare providers, including neurology NPs and PAs, may also participate. Learning ObjectivesAfter participating in the activity, learners should be better able toDescribe the role of FcRn in MG.Describe the efficacy of the treatment options for MG that target FcRn.Compare the safety of the treatment options for MG that target FcRn.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.50 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Dr. Nowak discloses the following relevant financial relationships with ineligible companies:Advisory Board/Consultant: Alexion (part of AstraZeneca), argenx, Amgen, Cour Pharmaceuticals, Immunovant, Janssen, UCBGrant/Research Support: Alexion (part of AstraZeneca), argenx, Amgen, Cour Pharmaceuticals, Immunovant, Janssen, UCBPlanners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Method of ParticipationThere are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you in within 30 days.Hardware/Software Requirements Windows Requirements: • Operating system: Windows XP Service Pack 2 or later • Browser: Internet Explorer 7 or later, Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionMacintosh Requirements: • Operating system: Mac OS X v10.3 or later • Browser: Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionPrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2024. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s). 

Jointly Provided by American Academy of CME Inc and CheckRare CE Inc.Support for this accredited continuing education activity has been made possible through an educational grant from argenx US Inc.and UCB.Estimated time to complete: 0.25 hoursStart date: November 7, 2024End date: November 6, 2025This quarter-hour CME-accredited program, hosted by Richard J. Nowak, MD, MS, explains the role of  neonatal fragment crystallizable receptor (FcRn) in myasthenia gravis (MG).To obtain CME credit, visit https://checkrare.com/learning/p-fcrn-and-myasthenia-gravis-pathophysiology/ Activity FacultyRichard J. Nowak, MD, MSDirector, Program in Clinical & Translational Neuromuscular Research (CTNR) Director, Yale Myasthenia Gravis Clinic Associate Professor of Neurology Division of Neuromuscular MedicineDepartment of Neurology Yale School of Medicine New Haven, CTTarget AudienceThis activity has been designed to meet the educational needs of physicians specializing in neurology and ophthalmology who may be involved in the diagnosis and care of individuals with MG. Other healthcare providers, including neurology NPs and PAs, may also participate. Learning ObjectivesAfter participating in the activity, learners should be better able toDescribe the role of FcRn in MG.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Faculty EducatorDr. Nowak discloses the following relevant financial relationships with ineligible companies:Advisory Board/Consultant: Alexion (part of AstraZeneca), argenx, Amgen, Cour Pharmaceuticals, Immunovant, Janssen, UCBGrant/Research Support: Alexion (part of AstraZeneca), argenx, Amgen, Cour Pharmaceuticals, Immunovant, Janssen, UCBPlanners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Method of ParticipationThere are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you in within 30 days.Hardware/Software Requirements Windows Requirements: • Operating system: Windows XP Service Pack 2 or later • Browser: Internet Explorer 7 or later, Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connection.Macintosh Requirements: • Operating system: Mac OS X v10.3 or later • Browser: Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionPrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2024. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s). 

Jointly Provided by the American Academy of CME and CheckRare CE Inc.Support for this accredited continuing education activity has been made possible through educational grant from argenx US Inc. and UCB.Estimated time to complete: 0.25 hoursStart date: November 7, 2024End date: November 6, 2025This quarter-hour CME-accredited program, hosted by Richard J. Nowak, MD, MS, discusses the safety and efficacy of neonatal fragment crystallizable receptor (FcRn)-directed therapies for patient with myasthenia gravis.To obtain CME credit, visit https://checkrare.com/learning/p-fcrn-and-myasthenia-gravis-treatment-options/ Activity FacultyRichard J. Nowak, MD, MSDirector, Program in Clinical & Translational Neuromuscular Research (CTNR) Director, Yale Myasthenia Gravis Clinic Associate Professor of Neurology Division of Neuromuscular MedicineDepartment of Neurology Yale School of Medicine New Haven, CTTarget AudienceThis activity has been designed to meet the educational needs of physicians specializing in neurology and ophthalmology who may be involved in the diagnosis and care of individuals with MG. Other healthcare providers, including neurology NPs and PAs, may also participate. Learning ObjectivesAfter participating in the activity, learners should be better able toDescribe the efficacy of the treatment options for MG that target FcRn.Compare the safety of the treatment options for MG that target FcRn.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Dr. Nowak discloses the following relevant financial relationships with ineligible companies:Advisory Board/Consultant: Alexion (part of AstraZeneca), argenx, Amgen, Cour Pharmaceuticals, Immunovant, Janssen, UCBGrant/Research Support: Alexion (part of AstraZeneca), argenx, Amgen, Cour Pharmaceuticals, Immunovant, Janssen, UCBPlanners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Method of ParticipationThere are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you in within 30 days.Hardware/Software Requirements Windows Requirements: • Operating system: Windows XP Service Pack 2 or later • Browser: Internet Explorer 7 or later, Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionMacintosh Requirements: • Operating system: Mac OS X v10.3 or later • Browser: Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionPrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2024. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s). 

This continuing education activity is provided by AffinityCE and CheckRare CE. This activity provides continuing education credit for physicians. A statement of participation is available for other attendees. Estimated time to complete: 0.50 hoursTo obtain CME credit, go to https://checkrare.com/learning/p-cushings-syndrome-treatment-research-highlights-endo-2024/Commercial SupportEducational Support for this activity was provided by Recordati Rare Diseases, Inc., and Xeris Pharmaceuticals.Learning ObjectiveAfter participating in the activity, learners should be better able to:Describe the latest research being presented to better manage individuals with Cushing's syndrome and its clinical relevance.Share new information with their clinical team. Activity DescriptionThis 30-minute CME program highlights the latest clinical research about Cushing's syndrome and Cushing' disease.Cushing's syndrome is rare endocrine disorder characterized by chronic hypercortisolism. It is often due to a pituitary adenoma producing excessive ACTH leading to hypercortisolism. Symptoms can range from mild to extensive.This CME program, hosted by Maria Fleseriu, MD, FACE, Professor of Medicine and Neurological Surgery, Director of the Pituitary Center at Oregon Health & Science University, provides an overview of the latest clinical research presented at ENDO 20234 involving Cushing's syndrome. FacultyMaria Fleseriu, MD, FACEProfessor of Medicine and Neurological SurgeryDirector of Pituitary CenterOregon Health & Science UniversityPortland, OregonDisclosure StatementAffinityCE and CheckRare CE staff, as well as planning and review committees, have no financial interests to disclose. Faculty EducatorsDr. Fleseriu discloses the following relevant financial relationships with ineligible companies to disclose:Funding to the University as Principle Investigator from Sparrow PharmaceuticalsScientific consultant for Crinetics Pharmaceuticals, Recordati Rare Diseases, Sparrow Pharmaceuticals, and Xeris PharmaceuticalsMitigation of Relevant Financial Relationships AffinityCE adheres to the ACCME's Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible companies. Method of ParticipationThere are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre- and post-program assessments. Your certificate will be emailed to you in within 30 days.Participation CostsThere is no cost to participate in this CME session. To receive CME credit for your participation, please complete the pre- and post-program assessments. Your certificate will be emailed to you in within 30 days.CME InquiriesFor all CME policy-related inquiries, please contact us at ce@affinityced.com.Send customer support requests to cds_support+ldrtc@affinityced.com.Copyright© 2024. This CME-certified activity is held as copyrighted © by AffinityCE and CheckRare CE. Through this notice, AffinityCE and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s). 

Yuliya Linhares, MD is a medical oncologist specializing in the comprehensive treatment of lymphoma and serves as chief of Lymphoma Services at Miami Cancer Institute. In this video, Dr. Linhares provides an overview of cutaneous T-cell lymphoma (CTCL) and discusses some strategies for shortening the diagnostic journey of this rare cancer.The diagnosis of CTCL is often challenging; as a result, delays in diagnosis (and subsequent work-up and treatment) can be significant. Part of the reason is the variability in how individual patients present with CTCL and its subtypes. Because mycosis fungoides progresses slowly, some patients may not experience progression beyond their initial symptoms, even beyond 10 years. Patients with mycosis fungoides or Sézary syndrome also have overlap in manifestations; in fact, Sézary syndrome was once classified as a malignant, leukemic variant of mycosis fungoides but is now recognized as a distinct CTCL subtype.Patients with mycosis fungoides may progress through three phases of skin symptoms. The first may feature little more than transient red, scaly areas of skin on the buttocks and torso. The plaques may be hyper- or hypopigmented. As such, these symptoms can be easily misidentified as common skin conditions such as eczema or psoriasis. The variability of signs and symptoms also adds to the challenge of making a timely, clear-cut diagnosis.In the second phase, patients with progressing disease may develop palpable, scaly, reddish-brown plaques that appear on any portion of the body. Over time, the affected areas of skin may grow, merging with other affected regions. Patients' skin presentation during this stage can vary considerably: Some patients may experience severe pruritus or pain in these scaly bumps, which can result in sleep disturbances and other challenges to quality of life. Other patients may remain asymptomatic other than the skin's appearance.Disease presentation is a bit more consistent in patients who have progressed to the third phase of skin symptoms. Some patients may develop mushroom-shaped skin tumors that can cause skin ulceration and infection. Even for patients with mycosis fungoides reaching this phase of skin progression, malignant spread is uncommon (only 10% will experience metastases to major organs).While patients with Stage III mycosis fungoides experience widespread erythema (over 80% of body surface area), erythroderma is a consistent feature of Sézary syndrome. This rash will often be associated with severe pruritus and peeling.In addition to erythroderma and B2 blood involvement, patients with Sézary syndrome will typically have several other characteristic signs: generalized lymphadenopathy, opportunistic infections, and alopecia. The liver and possibly the spleen will be enlarged, and patients often have very thick, coarse skin on the soles of the feet and palms of the hands (i.e., palmoplantar keratoderma).Diagnosis is usually made with a patient history, complete physical exam, blood tests, biopsy of skin lesions, computed tomography imaging, and sometimes lymph node biopsy and/or bone marrow biopsy. These methods can also be useful in determining the stage of disease, especially whether the lymph nodes have been involved and whether the cancerous cells have spread to blood and other organs. In addition to eczema and psoriasis, the differential diagnosis may include nonspecific dermatitis, lichen, lupus, pseudolymphoma, parapsoriasis, and toxidermia.To learn more about CTCL, visit our Cutaneous T-Cell Lymphoma (CTCL) Learning Center page. https://checkrare.com/cutaneous-t-cell-lymphoma-2/

Larisa Geskin, MD, Professor of Dermatology at Columbia University Medical Center and Director of the Comprehensive Skin Cancer Center at the Division of Cutaneous Oncology in the Department of Dermatology, discusses the challenges of diagnosing cutaneous T-cell lymphoma (CTCL).The diagnosis of CTCL is often challenging; as a result, delays in diagnosis (and subsequently work-up and treatment) can be significant. Part of the reason is the variability in how individual patients present with CTCL and its subtypes. Because mycosis fungoides progresses slowly, some patients may not experience progression beyond their initial symptoms, even beyond 10 years. Patients with mycosis fungoides or Sézary syndrome also have overlap in manifestations; in fact, Sézary syndrome was once classified as a malignant, leukemic variant of mycosis fungoides but is now recognized as a distinct CTCL subtype.Patients with mycosis fungoides may progress through three phases of skin symptoms. The first may feature little more than transient red, scaly areas of skin on the buttocks and torso. The plaques may be hyper- or hypopigmented. As such, these symptoms can be easily misidentified as common skin conditions such as eczema or psoriasis. The variability of signs and symptoms also adds to the challenge of making a timely, clear-cut diagnosis.In the second phase, patients with progressing disease may develop palpable, scaly, reddish-brown plaques that appear on any portion of the body. Over time, the affected areas of skin may grow, merging with other affected regions. Patients' skin presentation during this stage can vary considerably: Some patients may experience severe pruritus or pain in these scaly bumps, which can result in sleep disturbances and other challenges to quality of life. Other patients may remain asymptomatic other than the skin's appearance.Disease presentation is a bit more consistent in patients who have progressed to the third phase of skin symptoms. Some patients may develop mushroom-shaped skin tumors that can cause skin ulceration and infection. Even for patients with mycosis fungoides reaching this phase of skin progression, malignant spread is uncommon (only 10% will experience metastases to major organs).While patients with Stage III mycosis fungoides experience widespread erythema (over 80% of body surface area), erythroderma is a consistent feature of Sézary syndrome. This rash will often be associated with severe pruritus and peeling.In addition to erythroderma and B2 blood involvement, patients with Sézary syndrome will typically have several other characteristic signs: generalized lymphadenopathy, opportunistic infections, and alopecia. The liver and possibly the spleen will be enlarged, and patients often have very thick, coarse skin on the soles of the feet and palms of the hands (i.e., palmoplantar keratoderma).Diagnosis is usually made with a patient history, complete physical exam, blood tests, biopsy of skin lesions, computed tomography imaging, and sometimes lymph node biopsy and/or bone marrow biopsy. These methods can also be useful in determining the stage of disease, especially whether the lymph nodes have been involved and whether the cancerous cells have spread to blood and other organs. In addition to eczema and psoriasis, the differential diagnosis may include nonspecific dermatitis, lichen, lupus, pseudolymphoma, parapsoriasis, and toxidermia.To learn more about CTCL, visit our Cutaneous T-Cell Lymphoma (CTCL) Learning Center page. https://checkrare.com/ctcl-the-role-of-dermatologists-in-diagnosing-and-caring-for-patients/

Jointly Provided by American Academy of CME and CheckRare CE.Supported by educational grants from argenx US, Inc. and UCB Inc.To claim credit for this program, please visit https://checkrare.com/learning/p-myasthenia-gravis-research-highlights-aan-2024/Estimated time to complete: 0.5 hoursStart date: June 15, 2024End date: June 30,2025Activity DescriptionThis accredited CME program highlights the latest clinical research about myasthenia gravis, a rare, autoimmune disease that targets the neuromuscular junction.Treatment of myastheniagravis is highly individualized and depends greatly on the myasthenia gravis subtype of each patient as well as each patient's comorbidities. There are currently five drugs approved by the FDA, eculizumab, efgartigimod, ravulizumab, rozanolixizumab, and zilucoplan. Clinical trial data on these therapies, as well as real world data, were presented at the American Academy of Neurology Annual Meeting (AAN 2024) held in Denver, CO.This CME activity, hosted by Nicholas Silvestri, MD, of the University of Buffalo, provides an overview of the latest clinical research presented at AAN 2024 focused on myasthenia gravis.Activity FacultyNicholas Silvestri, MDProfessor of NeurologyUniversity of Buffalo Jacobs School of Medicine and Biomedical SciencesTarget AudienceThis activity has been designed to meet the educational needs of physicians specializing in neurology, ophthalmology, and general practice. Other members of the care team may also participate.Learning ObjectiveAfter participating in the activity, learners should be better able to:Describe the latest research being presented to better manage people with myasthenia gravis and its clinical relevanceAccreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Faculty EducatorDr. Silvestri discloses the following relevant financial relationships with ineligible companies:Advisory Board/Consultant: argenx, Alexion, UCB, Immunovant, Janssen, AmgenSpeakers Bureau: argenx, Alexion, UCB, TakedaPlanners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Method of ParticipationThere are no fees to participate in the activity.  Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you in within 30 days.PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.orgCopyright© 2024. American Academy of CME and CheckRare CE. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s). 

In this episode of our series focused on Fabry disease, we feature Maya Kineen, a patient and advocate with this rare disorder.Fabry disease is an inherited disorder that results from the buildup of a particular type of fat, called globotriaosylceramide, in the body's cells. Beginning in childhood, this buildup causes signs and symptoms that affect many parts of the body. Characteristic features of Fabry disease include episodes of pain, particularly in the hands and feet (acroparesthesias); clusters of small, dark red spots on the skin called angiokeratomas; a decreased ability to sweat (hypohidrosis); cloudiness of the front part of the eye (corneal opacity); problems with the gastrointestinal system; ringing in the ears (tinnitus); and hearing loss. Fabry disease also involves potentially life-threatening complications such as progressive kidney damage, heart attack, and stroke. Some affected individuals have milder forms of the disorder that appear later in life and affect only the heart or kidneys.

This is the second of a three-part series focusing on Fabry disease. In this episode, we talk with Nicola Longo, MD, Chief of the Division of Medical Genetics at the University of Utah, Spencer Fox Eccles School of Medicine in Salt Lake City. Dr. Longo discusses Fabry disease, including the progression of the disease and personalized medicine.Fabry disease is an inherited disorder that results from the buildup of globotriaosylceramide or GL-3. The disorder affects many parts of the body. Signs and symptoms may include acroparesthesias, angiokeratomas, hypohidrosis, corneal opacity, and hearing loss. Potentially severe complications can include progressive kidney damage, heart attack, and stroke. Fabry disease is caused by mutations in the GLA gene and is inherited in an X-linked manner. Treatment may include enzyme replacement therapy (ERT); pain medications, ACE inhibitors; and chronic hemodialysis or renal transplantation for end stage renal disease.

In this first part of our four-part series on Fabry disease, we feature William Burns, MD, a biochemical geneticist at Greenwood Genetic Center in Greenwood, South Carolina. Dr. Burns summarizes this rare disease, including current management strategies.Fabry disease is a lysosomal storage disorder, meaning that a glycosphingolipid called GL-3 accumulates in the lysosomes, causing tissue damage; many cell types are affected.The disease is caused by mutations in the GLA gene, resulting in nonfunctional or dysfunctional alpha-galactosidase A, a lysosomal enzyme. The mutations can be inherited, so multiple family members can have the disease.Fabry disease is a multisystemic disease, affecting many organs, including the heart, kidney and nervous system, resulting in life-threatening complications and a reduced life expectancy. Early signs of the disease start in childhood and adolescence, but it is a progressive, lifelong condition.Newborn screening has now been performed in several countries, yielding a prevalence ranging from 1 in 1,368 to 1 in 8,882 births.

Ozlem Goker-Alpan, MD, Founder and President, LDRTC and David G. Warnock, MD. Professor of Medicine (Emeritus) at University of Alabama at Birmingham discuss best practices to identify and treat kidney problems associated with lysosomal disorders.This CME/CE activity describes the pathophysiologies and management options for lysosomal disease patients with kidney problems. This continuing education activity is provided through collaboration between the Lysosomal and Rare Disorders Research and Treatment Center (LDRTC), CheckRare CE, and AffinityCE. This activity provides continuing education credit for physicians, physician assistants, nurses, nurse practitioners, and genetic counselors. A statement of participation is available to other attendees. To receive credit for this program, go to https://checkrare.com/learning/ Speakers Ozlem Goker-Alpan, MD, Founder and President, LDRTC David G. Warnock, MD. Professor of Medicine (Emeritus)University of Alabama at BirminghamDisclosuresAffinityCE staff, LDRTC staff, CheckRare staff, planners, and reviewers, have no relevant financial interests to disclose. All faculty disclosures are listed below and are included in the beginning of each presentation.Dr. Goker-Alpan is a consultant, a principal investigator and /or on the speaker bureau, or has received grant support, from the following pharmaceutical companies: Actelion, Amicus Therapeutics, Sanofi, Takeda, Pfizer/Protalix.Dr. Warnock has had research support and/or consulting arrangements with Genzyme Corporation (Sanofi), Shire LLC (Takeda), Amicus, Protalix and Chiesi, Zebra Bio, Walking Fish, Hanmi, and Vera Therapeutics.Mitigation of Relevant Financial RelationshipsAffinityCE adheres to the ACCME's Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of the activity. Conflicts of interest for presenting faculty with relevant financial interests were resolved through peer review of content by a non-conflicted reviewer.Learning ObjectivesAt the end of this activity, participants should be able to:Describe the role of the nephrologist in the team approach to careDescribe best practices to monitor kidney function in lysosomal disordersDescribe best practices to treat kidney disorders lysosomal disordersSupport for this educational activity was provided by Takeda, Sanofi, Amicus Therapeutics and Chiesi USA.

This 16-minute CME-accredited program, hosted by Aleena Banerji, MD, Associate Professor at Harvard Medical School and Clinical Director of the Massachusetts General Hospital ( MGH) Allergy and Immunology Unit, highlights the future treatment options for patients with hereditary angioedema (HAE) presented at ACAAI 2023. Jointly Provided by American Academy of CME and CheckRare CE. Support for this accredited continuing education activity has been made possible through educational grant from Ionis Pharmaceuticals Inc. Estimated time to complete: 0.25 hours Start date: January 31, 2024 End date: January 30, 2025To obtain CME credit, go to https://checkrare.com/learning/p-hae-treatment-advances-highlights-from-acaai/Activity Faculty Aleena Banerji, MD Associate Professor Clinical Director, MGH Allergy and Immunology Unit Harvard Medical School Massachusetts General Hospital Boston, MA Target Audience This activity has been designed to meet the educational needs of physicians specializing in allergy medicine, immunology, internal medicine, and pediatrics who may be involved in the care for individuals with HAE. Other healthcare providers (HCPs) may also participate. Learning Objectives After participating in the activity, learners should be better able to • Understand clinical data of treatments in development for HAE Accreditation and Credit Designation In support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physicians American Academy of CME, Inc., designates this enduring material for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPs Other members of the care team will receive a certificate of participation. Disclosure Statement According to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated. Disclosure of relevant financial relationships are as follows: Faculty Educator Dr. Banerji discloses the following relevant financial relationships with ineligible companies: • Research Grant: Takeda, Ionis Pharmaceuticals, Astria • Advisory Board: Takeda, BioCryst, Astria, Intellia, CSL Behring, KalVista, ADARx Planners for this activity have no relevant financial relationships with any ineligible companies. This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information. Method of Participation There are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments at https://checkrare.com/learning/p-hae-treatment-advances-highlights-from-acaai/ Your certificate will be emailed to you in within 30 days. Privacy For more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ Contact For any questions, please contact: CEServices@academycme.org Copyright © 2024. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

This 25-minute CME-accredited program, hosted by Aleena Banerji, MD, Associate Professor at Harvard Medical School and Clinical Director of the Massachusetts General Hospital ( MGH) Allergy and Immunology Unit, highlights the current treatment options for patients with hereditary angioedema (HAE). Jointly Provided by American Academy of CME and CheckRare CE. Support for this accredited continuing education activity has been made possible through educational grant from Ionis Pharmaceuticals Inc. Estimated time to complete: 0.50 hours Start date: January 31, 2024 End date: January 30, 2025To obtain CME credit, go to https://checkrare.com/learning/p-hereditary-angioedema-current-treatment-options/Activity Faculty Aleena Banerji, MD Associate Professor Clinical Director, MGH Allergy and Immunology Unit Harvard Medical School Massachusetts General Hospital Boston, MA Target Audience This activity has been designed to meet the educational needs of physicians specializing in allergy medicine, immunology, internal medicine, and pediatrics who may be involved in the care for individuals with HAE. Other healthcare providers (HCPs) may also participate. Learning Objectives After participating in the activity, learners should be better able to • Review current guidelines and unmet needs of patients with HAE Accreditation and Credit Designation In support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physicians American Academy of CME, Inc., designates this enduring material for a maximum of 0.50 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPs Other members of the care team will receive a certificate of participation. Disclosure Statement According to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated. Disclosure of relevant financial relationships are as follows: Faculty Educator Dr. Banerji discloses the following relevant financial relationships with ineligible companies: • Research Grant: Takeda, Ionis Pharmaceuticals, Astria • Advisory Board: Takeda, BioCryst, Astria, Intellia, CSL Behring, KalVista, ADARx Planners for this activity have no relevant financial relationships with any ineligible companies. This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information. Method of Participation There are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments at https://checkrare.com/learning/p-hereditary-angioedema-current-treatment-options/ Your certificate will be emailed to you in within 30 days. Privacy For more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ Contact For any questions, please contact: CEServices@academycme.org Copyright © 2024. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

Ozlem Goker-Alpan, MD of LDRTC and John Bach, MD, Professor of Neurology at Rutgers School of Medicine discuss best practices to manage respiratory complications in persons with lysosomal disorders.This continuing education activity is provided through collaboration between the Lysosomal and Rare Disorders Research and Treatment Center (LDRTC), CheckRare CE, and AffinityCE. This activity provides continuing education credit for physicians, physician assistants, nurses, nurse practitioners, and genetic counselors. A statement of participation is available to other attendees. To receive credit for this program, visit https://checkrare.com/learning/p-ldrtc2023-webinar3-assessing-monitoring-managing-respiratory-involvement-in-lysosomal-disorders/DisclosuresAffinityCE staff, LDRTC staff, CheckRare staff, planners, and reviewers, have no relevant financial interests to disclose. All faculty disclosures are listed below and are included in the beginning of each presentation.Ozlem Goker-Alpan, MDFounder and President, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC).Dr. Goker-Alpan is a consultant, a principal investigator and /or on the speaker bureau, or has received grant support, from the following pharmaceutical companies: Actelion, Amicus Therapeutics, Sanofi, Takeda, Pfizer/Protalix.John Bach, MDProfessor of Physical Medicine and Rehabilitation, Professor of Neurology, Rutgers New Jersey Medical Center.Dr. Bach has no relevant financial interest to disclose.Mitigation of Relevant Financial Relationships AffinityCE adheres to the ACCME's Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of the activity. Conflicts of interest for presenting faculty with relevant financial interests were resolved through peer review of content by a non-conflicted reviewer.Learning ObjectivesAt the end of this activity, participants should be able to:• Describe the most common LSDs that have pulmonary complications. • Describe best practices to manage pulmonary symptoms in Pompe disease. • Describe best practices to manage pulmonary symptoms in MPSs.• Describe best practices to manage sleep apnea in lysosomal diseases.PhysiciansThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.AffinityCE designates this enduring activity for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Physician AssistantsAffinityCE designates this enduring activity for a maximum of 1.25 AMA PRA Category 1 Credits™. Physician Assistants should claim only the credit commensurate with the extent of their participation in the activity.NursesContinuing Nursing Education is provided for this program through the joint providership of AffinityCE and the LDRTC. AffinityCE is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation (ANCC). This activity provides a maximum of 1.25 hours of continuing nursing education credit.Nurse PractitionersAffinityCE designates this enduring activity for a maximum of 1.25 AMA PRA Category 1 Credits™. Nurse practitioners should claim only the credit commensurate with the extent of their participation in the activity.Genetic Counselors Category 2 CEUAffinityCE designates this enduring activity for a maximum of 1.25 AMA PRA Category 1 Credit™. Genetic counselors should claim only the credit commensurate with the extent of their participation in the activity.Other ProfessionalsAll other health care professionals completing this continuing education activity will be issued a statement of participation indicating the number of hours of continuing education credit. This may be used for professional education CE credit. Please consult your accrediting organization or licensing board for their acceptance of this CE activity.Commercial Support Support for this educational activity was provided by Takeda, Sanofi, Amicus Therapeutics and Chiesi USA. Participation CostsThere is no cost to participate in this activity.CME InquiriesFor all CME policy-related inquiries, please contact us at ce@affinityced.com.Send customer support requests to cds_support+ldrtc@affinityced.com.

This 40-minute CME-accredited program, hosted by Aleena Banerji, MD, Associate Professor at Harvard Medical School and Clinical Director of the Massachusetts General Hospital ( MGH) Allergy and Immunology Unit, highlights the current and future treatment options for patients with hereditary angioedema (HAE). Jointly Provided by American Academy of CME and CheckRare CE. Support for this accredited continuing education activity has been made possible through educational grant from Ionis Pharmaceuticals Inc. Estimated time to complete: 0.75 hours Start date: January 31, 2024 End date: January 30, 2025To obtain CME credit, go to https://checkrare.com/learning/p-hereditary-angioedema-current-and-future-treatment-options/ Activity Faculty Aleena Banerji, MD Associate Professor Clinical Director, MGH Allergy and Immunology Unit Harvard Medical School Massachusetts General Hospital Boston, MA Target Audience This activity has been designed to meet the educational needs of physicians specializing in allergy medicine, immunology, internal medicine, and pediatrics who may be involved in the care for individuals with HAE. Other healthcare providers (HCPs) may also participate. Learning Objectives After participating in the activity, learners should be better able to • Review current guidelines and unmet needs of patients with HAE • Understand clinical data of treatments in development for HAE Accreditation and Credit Designation In support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physicians American Academy of CME, Inc., designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPs Other members of the care team will receive a certificate of participation. Disclosure Statement According to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated. Disclosure of relevant financial relationships are as follows: Faculty Educator Dr. Banerji discloses the following relevant financial relationships with ineligible companies: • Research Grant: Takeda, Ionis Pharmaceuticals, Astria • Advisory Board: Takeda, BioCryst, Astria, Intellia, CSL Behring, KalVista, ADARx Planners for this activity have no relevant financial relationships with any ineligible companies. This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information. Method of Participation There are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments at https://checkrare.com/learning/p-hereditary-angioedema-current-and-future-treatment-options/ Your certificate will be emailed to you in within 30 days. Privacy For more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ Contact For any questions, please contact: CEServices@academycme.org Copyright © 2024. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

In this final episode of our four-part series focused on alpha-mannosidosis, we feature Rhonda Skipper, a mom of two boys, Dale and Matt, who have this rare disease.Alpha-mannosidosis is a rare genetic disorder characterized by a deficiency of the enzyme alpha-D-mannosidase. Alpha-mannosidosis is best thought of as a continuum of disease that is generally broken down into three forms: a mild, slowly progressive form (type 1); a moderate form (type 2); and a severe, often rapidly progressive and potentially life-threatening form (type 3).The symptoms and severity of the disorder are highly variable. Signs may include distinctive facial features, skeletal abnormalities, hearing loss, intellectual disability, and dysfunction of the immune system. Alpha-mannosidosis is caused by mutations of the MAN2B1 gene. This genetic mutation is inherited as an autosomal recessive trait.

This is the third of a four-part series focusing on alpha-mannosidosis. In this episode, we feature Dr. Markey McNutt, who will focus on the challenges of identifying and caring for patients with this rare disease. Dr. McNutt is a Clinical Geneticist at the University of Texas Southwestern Medical Center in Dallas.Alpha-mannosidosis is a rare genetic disorder characterized by a deficiency of the enzyme alpha-D-mannosidase. Alpha-mannosidosis is best thought of as a continuum of disease that is generally broken down into three forms: a mild, slowly progressive form (type 1); a moderate form (type 2); and a severe, often rapidly progressive and potentially life-threatening form (type 3).The symptoms and severity of the disorder are highly variable. Signs may include distinctive facial features, skeletal abnormalities, hearing loss, intellectual disability, and dysfunction of the immune system. Alpha-mannosidosis is caused by mutations of the MAN2B1 gene. This genetic mutation is inherited as an autosomal recessive trait.

This is the second of a four-part series focusing on alpha-mannosidosis. In this episode, we talk with Dr. Reid Sutton on the challenges of recognizing this rare disease, focusing on the signs and symptoms. Dr. Sutton is a Clinical Geneticist and a Clinical Biochemical Geneticist at Baylor College of Medicine and Texas Children's Hospital in Houston.Alpha-mannosidosis is a rare genetic disorder characterized by a deficiency of the enzyme alpha-D-mannosidase. Alpha-mannosidosis is best thought of as a continuum of disease that is generally broken down into three forms: a mild, slowly progressive form (type 1); a moderate form (type 2); and a severe, often rapidly progressive and potentially life-threatening form (type 3).The symptoms and severity of the disorder are highly variable. Signs may include distinctive facial features, skeletal abnormalities, hearing loss, intellectual disability, and dysfunction of the immune system. Alpha-mannosidosis is caused by mutations of the MAN2B1 gene. This genetic mutation is inherited as an autosomal recessive trait.

In this first part of our four-part series on alpha-mannosidosis, we feature Laura Buch, a physician assistant who practices medical genetics at the Greenwood Genetic Center in South Carolina. Laura's work focuses on the diagnosis and treatment of patients with abnormal newborn screens, inborn errors of metabolism, and lysosomal storage disorders. She also cares for alpha-mannosidosis patients.Alpha-mannosidosis is a rare genetic disorder characterized by a deficiency of the enzyme alpha-D-mannosidase. Alpha-mannosidosis is best thought of as a continuum of disease that is generally broken down into three forms: a mild, slowly progressive form (type 1); a moderate form (type 2); and a severe, often rapidly progressive and potentially life-threatening form (type 3).The symptoms and severity of the disorder are highly variable. Signs may include distinctive facial features, skeletal abnormalities, hearing loss, intellectual disability, and dysfunction of the immune system. Alpha-mannosidosis is caused by mutations of the MAN2B1 gene. This genetic mutation is inherited as an autosomal recessive trait.

This 30-minute CME-accredited program highlights the connection between the complement system and myasthenia gravis in regards to the treatment of this rare disease. Jointly Provided by American Academy of CME and CheckRare CE. Support for this accredited continuing education activity has been made possible through educational grant from UCB. Start date: December 18, 2023. End date: December 18, 2024 To receive CME credit, go to https://checkrare.com/learning/p-myasthenia-gravis-and-the-complement-system-treatment-options/ Activity FacultyJames F Howard Jr, MDProfessor of Neurology, Medicine & Allied Health Department of NeurologyThe University of North Carolina at Chapel HillTarget AudienceThis activity has been designed to meet the educational needs of physicians specializing in neurology who may be involved in the diagnosis and care for individuals with TIO. Other healthcare providers, including neurology NPs and PAs, may also participate. Learning ObjectivesAfter participating in the activity, learners should be better able toDescribe efficacy of the treatment options for MG that target the complement system.Compare the safety of the treatment options for MG that target the complement system.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Faculty EducatorDr. Howard discloses the following relevant financial relationships with ineligible companies:Grant/Research support (paid to his institution): Alexion Pharmaceuticals, argenx, Cartesian Therapeutics, Centers for Disease Control and Prevention, Myasthenia Gravis Foundation of America, Muscular Dystrophy Association, National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), Patient-Centered Outcomes Research Institute, and Ra Pharmaceuticals (now UCB Biosciences).Advisory Board/Consultant: Alexion Pharmaceuticals, argenx, Biologix Pharma, F. Hoffman-LaRoche Ltd, Immunovant Inc., Merck EMD Serono, NMD Pharma, Novartis Pharmaceuticals, Ra Pharmaceuticals (now UCB Biosciences), Regeneron Pharmaceuticals, Sanofi US, Horizon Therapeutics (now Amgen) Toleranzia AB, and Zai Labs. Shareholder (as part of a family trust): Johnson & Johnson, Pfizer, General Electric, GE Healthcare, GlaxoSmithKline, ViatrisNon-financial Support (meeting travel): Alexion Pharmaceuticals, argenx, Ra Pharmaceuticals (now UCB Biosciences), Toleranzia AB.Planners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Method of ParticipationThere are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you in within 30 days.Hardware/Software Requirements Windows Requirements: • Operating system: Windows XP Service Pack 2 or later • Browser: Internet Explorer 7 or later, Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionMacintosh Requirements: • Operating system: Mac OS X v10.3 or later • Browser: Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionPrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.org Copyright© 2023. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

This 15-minute CME-accredited program highlights the connection between the complement system and myasthenia gravis in regards to the pathophysiology of this rare disease. Jointly Provided by American Academy of CME and CheckRare CE. Support for this accredited continuing education activity has been made possible through educational grant from UCB. Start date: December 18, 2023. End date: December 18, 2024 To receive CME credit, go to https://checkrare.com/learning/p-myasthenia-gravis-and-the-complement-system-pathophysiology/ Activity FacultyJames F Howard Jr, MDProfessor of Neurology, Medicine & Allied Health Department of NeurologyThe University of North Carolina at Chapel HillTarget AudienceThis activity has been designed to meet the educational needs of physicians specializing in neurology who may be involved in the diagnosis and care for individuals with TIO. Other healthcare providers, including neurology NPs and PAs, may also participate. Learning ObjectivesAfter participating in the activity, learners should be better able toDescribe efficacy of the treatment options for MG that target the complement system.Compare the safety of the treatment options for MG that target the complement system.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Faculty EducatorDr. Howard discloses the following relevant financial relationships with ineligible companies:Grant/Research support (paid to his institution): Alexion Pharmaceuticals, argenx, Cartesian Therapeutics, Centers for Disease Control and Prevention, Myasthenia Gravis Foundation of America, Muscular Dystrophy Association, National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), Patient-Centered Outcomes Research Institute, and Ra Pharmaceuticals (now UCB Biosciences).Advisory Board/Consultant: Alexion Pharmaceuticals, argenx, Biologix Pharma, F. Hoffman-LaRoche Ltd, Immunovant Inc., Merck EMD Serono, NMD Pharma, Novartis Pharmaceuticals, Ra Pharmaceuticals (now UCB Biosciences), Regeneron Pharmaceuticals, Sanofi US, Horizon Therapeutics (now Amgen) Toleranzia AB, and Zai Labs. Shareholder (as part of a family trust): Johnson & Johnson, Pfizer, General Electric, GE Healthcare, GlaxoSmithKline, ViatrisNon-financial Support (meeting travel): Alexion Pharmaceuticals, argenx, Ra Pharmaceuticals (now UCB Biosciences), Toleranzia AB.Planners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Method of ParticipationThere are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you in within 30 days.Hardware/Software Requirements Windows Requirements: • Operating system: Windows XP Service Pack 2 or later • Browser: Internet Explorer 7 or later, Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionMacintosh Requirements: • Operating system: Mac OS X v10.3 or later • Browser: Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionPrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/Contact: CEServices@academycme.orgCopyright© 2023. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

This 45-minute CME-accredited program highlights the connection between the complement system and myasthenia gravis in regards to the pathophysiology and treatment of this rare disease. Jointly Provided by American Academy of CME and CheckRare CE. Support for this accredited continuing education activity has been made possible through educational grant from UCB. Start date: December 18, 2023. End date: December 18, 2024 To receive CME credit, go to https://checkrare.com/learning/p-myasthenia-gravis-and-the-complement-system/ Activity FacultyJames F Howard Jr, MDProfessor of Neurology, Medicine & Allied Health Department of NeurologyThe University of North Carolina at Chapel HillTarget AudienceThis activity has been designed to meet the educational needs of physicians specializing in neurology who may be involved in the diagnosis and care for individuals with TIO. Other healthcare providers, including neurology NPs and PAs, may also participate. Learning ObjectivesAfter participating in the activity, learners should be better able toDescribe efficacy of the treatment options for MG that target the complement system.Compare the safety of the treatment options for MG that target the complement system.Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation.Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows:Faculty EducatorDr. Howard discloses the following relevant financial relationships with ineligible companies:Grant/Research support (paid to his institution): Alexion Pharmaceuticals, argenx, Cartesian Therapeutics, Centers for Disease Control and Prevention, Myasthenia Gravis Foundation of America, Muscular Dystrophy Association, National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), Patient-Centered Outcomes Research Institute, and Ra Pharmaceuticals (now UCB Biosciences).Advisory Board/Consultant: Alexion Pharmaceuticals, argenx, Biologix Pharma, F. Hoffman-LaRoche Ltd, Immunovant Inc., Merck EMD Serono, NMD Pharma, Novartis Pharmaceuticals, Ra Pharmaceuticals (now UCB Biosciences), Regeneron Pharmaceuticals, Sanofi US, Horizon Therapeutics (now Amgen) Toleranzia AB, and Zai Labs. Shareholder (as part of a family trust): Johnson & Johnson, Pfizer, General Electric, GE Healthcare, GlaxoSmithKline, ViatrisNon-financial Support (meeting travel): Alexion Pharmaceuticals, argenx, Ra Pharmaceuticals (now UCB Biosciences), Toleranzia AB.Planners for this activity have no relevant financial relationships with any ineligible companies.This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.Method of ParticipationThere are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments. Your certificate will be emailed to you in within 30 days.Hardware/Software Requirements Windows Requirements: • Operating system: Windows XP Service Pack 2 or later • Browser: Internet Explorer 7 or later, Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionMacintosh Requirements: • Operating system: Mac OS X v10.3 or later • Browser: Mozilla Firefox 2.5 or later • Internet connection: DSL, cable modem, or other high-speed connectionPrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/Contact: CEServices@academycme.orgCopyright© 2023. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

Jointly Provided by American Academy of CME and CheckRare CE Support for this accredited continuing education activity has been made possible through an educational grant from Kyowa Kirin. Estimated time to complete: 0.25 hours Start date: November 30, 2023 End date: November 30, 2024 This 15-minute CME-accredited program, hosted by Aliya Khan, MD, Clinical Professor of Medicine at McMaster University, highlights the best practices to diagnose tumor induced osteomalacia (TIO) based on the recently published guidelines in the Journal of Internal Medicine. To earn credit, go to https://checkrare.com/learning/p-new-guidance-to-treat-tumor-induced-osteomalacia-tio-2023-3/ Activity Faculty Aliya Khan MD, FRCPC, FACP, FACE, FASBMR Clinical Professor of Medicine Director, Calcium Disorders Clinic Director, Fellowship in Metabolic Bone Disease McMaster University Target Audience This activity has been designed to meet the educational needs of physicians specializing in neurology, orthopedics, internal medicine/general practice, rheumatology, endocrinology, pain management, and radiology, who may be involved in the care for individuals with TIO. Other healthcare providers may also participate. Learning Objectives After participating in the activity, learners should be better able to • Describe the latest recommendations for treating patients with TIOAccreditation and Credit Designation In support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physicians American Academy of CME, Inc., designates this enduring material for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPs Other members of the care team will receive a certificate of participation. Disclosure Statement According to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated. Disclosure of relevant financial relationships are as follows: Faculty Educator Dr. Khan discloses the following relevant financial relationships with ineligible companies to disclose: • Advisory Board/Consultant: Amgen, Ascendis, Alexion • Grant/Research support: Ascendis, Alexion, Amolyt • Speakers Bureaus: Amgen, Ascendis, Alexion Planners for this activity have no relevant financial relationships with any ineligible companies. This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information. Method of Participation There are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments at: https://checkrare.com/learning/p-new-guidance-to-treat-tumor-induced-osteomalacia-tio-2023-3/Your certificate will be emailed to you in within 30 days. Privacy For more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ Contact For any questions, please contact: CEServices@academycme.org Copyright © 2023. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).

Jointly Provided by American Academy of CME and CheckRare CE Support for this accredited continuing education activity has been made possible through educational grant from Kyowa Kirin. Estimated time to complete: 0.25 hours Start date: November 30, 2023 End date: November 30, 2024 This 15-minute CME-accredited program, hosted by Aliya Khan, MD, Clinical Professor of Medicine at McMaster University, highlights the best practices to diagnose tumor induced osteomalacia (TIO) based on the recently published guidelines in the Journal of Internal Medicine. To earn credit, go to https://checkrare.com/learning/p-new-guidance-to-diagnose-tumor-induced-osteomalacia-tio-2023-2/Activity Faculty Aliya Khan MD, FRCPC, FACP, FACE, FASBMR Clinical Professor of Medicine Director, Calcium Disorders Clinic Director, Fellowship in Metabolic Bone Disease McMaster University Target Audience This activity has been designed to meet the educational needs of physicians specializing in neurology, orthopedics, internal medicine/general practice, rheumatology, endocrinology, pain management, and radiology, who may be involved in the care for individuals with TIO. Other healthcare providers may also participate. Learning Objectives After participating in the activity, learners should be better able to • Describe the latest recommendations for diagnosing patients with TIOAccreditation and Credit Designation In support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. is Jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physicians American Academy of CME, Inc., designates this enduring material for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPs Other members of the care team will receive a certificate of participation. Disclosure Statement According to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated. Disclosure of relevant financial relationships are as follows: Faculty Educator Dr. Khan discloses the following relevant financial relationships with ineligible companies to disclose: • Advisory Board/Consultant: Amgen, Ascendis, Alexion • Grant/Research support: Ascendis, Alexion, Amolyt • Speakers Bureaus: Amgen, Ascendis, Alexion Planners for this activity have no relevant financial relationships with any ineligible companies. This activity will review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information. Method of Participation There are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please complete the pre and post-program assessments at: https://checkrare.com/learning/p-new-guidance-to-diagnose-tumor-induced-osteomalacia-tio-2023-2/Your certificate will be emailed to you in within 30 days. Privacy For more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ Contact For any questions, please contact: CEServices@academycme.org Copyright © 2023. This CME-certified activity is held as copyrighted © by American Academy of CME and CheckRare CE. Through this notice, the Academy and CheckRare CE grant permission of its use for educational purposes only. These materials may not be used, in whole or in part, for any commercial purposes without prior permission in writing from the copyright owner(s).