CReATe Connect Podcast

Dr. Terry Heiman-Patterson is a neurologist and professor at Temple University and the director of the Center for Neurodegenerative Disorders and the MDA/ALS Center of Hope.  Dr. Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami.  In this podcast they will be discussing their recent publication “Guidance for clinical management of pathogenic variant carriers at elevated genetic risk for ALS/FTD”.

Dr. Ruben van Eijk is an associate professor in the Department of Neurology at the University Medical Center Utrecht in the Netherlands as well as a statistical consultant and medical statistician for the clinical trial methodology group at the Julius Center also in Utrecht.  Dr. Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami.  They will be discussing their recent publication “Rethinking phase 2 trials in amyotrophic lateral sclerosis”.

Dr. Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami.  Here he discusses the recent publication “Prognostic clinical and biological markers for amyotrophic lateral sclerosis disease progression: validation and implications for clinical trial design and analysis”.

Dr. Jesse Crayle is a clinical neuromuscular fellow in the Department of Neurology at Washington University in St. Louis and Dr. Evadnie Rampersaud is a Principal Bioinformatics Research Scientist at St. Jude Children's Research Hospital.  They will be discussing their publication “Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype.”

Nuedexta is a combination of dextromethorphan and quinidine, and is FDA approved for treating “pseudobulbar affect” (a symptom complex where patients lose control of their laughing and crying).  Here we summarize recent trials suggesting that Nuedexta might also help bulbar function (speech, swallowing and oral secretions).  We also discuss important risks, monitoring, and insurance coverage.

Lions Mane is a mushroom that has neuroprotective, neurotrophic, antioxidant, and anti-inflammatory properties.  Here we review what is known about its use in ALS models as well as patients living with the disease.

Insulin is a hormone most commonly used to lower blood sugar in people with diabetes.  Here we talk about some theoretical ways it might help help people with ALS, as well as the lack of convincing case reports or trials and the risks.

Caffeine is a chemical most of us ingest every day.  In addition to its stimulant properties, there are some theoretical ways it could help slow ALS progression.  Here we discuss the contradictory pre-clinical models and the lack of a convincing relationship between caffeine intake and ALS progression in natural history studies.

Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami. Here he discusses the recent publication “The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology”. 

Dr. Caroline McHutchison is a Neuropsychologist and CReATe Clinical Research Scholar at the University of Edinburgh and Dr. Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami. They will be discussing their recent publication “Temporal course of cognitive and behavioural changes in motor neuron diseases”.

Dr. Chad Heatwole is a Professor of Neurology and the Director of the Center for Health and Technology at the University of Rochester Medical Center and Dr. Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami. They will be discussing their recent publication “The amyotrophic lateral sclerosis-health index (ALS-HI): development and evaluation of a novel outcome measure” and its role as a patient reported outcome measure for ALS.

Sodium chlorite is an experimental drug targeting macrophage activation. It exists in different formulations. An oral formulation has potentially deadly side effects. An IV formulation called NP001 has been in recent trials targeting a subset of people with ALS. Here we review the interesting development of this product and where we expect that to go in the near future.

Rituximab is an intravenous product that reduces B lymphocytes. It can help improve strength in patients with myasthenia gravis and multi-focal motor neuropathy, neuromuscular diseases that are caused by circulating antibodies made by B lymphocytes. In this podcast we examine the possible use of rituximab to treat patients with ALS

Ozone is an oxidizing agent which has some surprisingly plausible mechanisms by which it could influence ALS progression. It can also be dangerous. The FDA has warned against using it as a treatment for any disease. Further studies are needed to determine whether there is any dose or route of administration that might be safe and effective for use in people with ALS.

Astaxanthin is a naturally occurring chemical which has plausible mechanisms for treating ALS and appears reasonably safe and well tolerated in non-ALS trials. We look forward to ALS-specific trials planned later this year which should shed important light on whether this is specifically safe for people with ALS, and whether it really can slow ALS progression.

Dr. Martin Turner is a Professor of Clinical Neurology & Neurosciences at the University of Oxford and Dr. Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami. They will be discussing their recent publication “Neurofilament light chain in drug development for amyotrophic lateral sclerosis: a critical appraisal”, and the potential role of NfL as a biomarker for ALS. This is part I of a two part series.

Dr. Martin Turner is a Professor of Clinical Neurology & Neurosciences at the University of Oxford and Dr. Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami. They will be discussing their recent publication “Neurofilament light chain in drug development for amyotrophic lateral sclerosis: a critical appraisal”, and the potential role of NfL as a biomarker for ALS. This is part II of a two part series.

There is a theorized association between mycobacteria and ALS, and two published case reports described improvements in ALS-like conditions (both with atypical features) after treatment with antimycobacterial antibiotics. Here we review these in detail and discuss our thoughts on how they might change our approach in certain patients in the future.

Corticosteroids are a class of medications with well-studied effects on the immune system and some people living with ALS have reported benefits from them online. Here we review the pre-clinical and clinical data. We conclude that there is currently no clear evidence that steroids can slow ALS progression, and they can have many side effects.

Butyrates have plausible mechanisms for slowing ALS progression and positive pre-clinical studies. One trial suggests that sodium phenylbutyrate (NaPB) in combination with Tauroursodeoxycholic acid (TUDCA) can slow ALS progression and prolong survival, but the specific contribution of NaPB toward this effect is unclear. Butyrates appear reasonably safe for use in humans. Based on the above information, we support a trial of a butyrate in PALS, but we cannot yet recommend one as a treatment.

Methylcobalamin is a specific precursor to B12 (cobalamin). It has promising mechanisms by which it could slow ALS progression. Two trials done in Japan suggest that 50mg via intramuscular injection twice weekly can slow ALS progression and prolong survival. Here we discuss the evidence for ultra-high dose methylcobalamin in patients with ALS and conclude that it may offer benefit, but only if administered within the first year of symptoms. If started after the first year, there is no evidence of benefit. It appears reasonably safe.

Dr. Jim Caress is a Professor of Neurology at Wake Forest University and Dr. Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami. They will be discussing their recent publication titled “Harnessing the power of the electronic health record for ALS research and quality improvement: CReATe CAPTURE-ALS and the ALS Toolkit”.

Dr. Mary-Louise Rogers is an Associate Professor at the College of Medicine and Public Health at Flinders University and Dr. Michael Benatar is a Professor of Neurology and Chief of the Neuromuscular Division and Executive Director of the ALS Center at the University of Miami. They will be discussing their recent publication titled “Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis,” which discusses the importance of biomarkers in ALS.

Dr. Marc Weisskopf is the Cecil K. and Philip Drinker Professor of Environmental Epidemiology and Physiology at Harvard T. H. Chan School of Public Health. In this interview, he discusses his recent publication titled “Occupational lead exposure and survival with amyotrophic lateral sclerosis,” which discusses the role that environmental risk factors could play in ALS.

Dr. Melissa Nel is a Research Fellow, and Dr. Jeannine Heckmann a Professor of Neurology, both at the University of Cape Town in South Africa. In this interview, they discuss their recent publication titled “Revealing the Mutational Spectrum in South Africans with Amyotrophic Lateral Sclerosis” which highlights that ALS patients of African genetic ancestry should be included in large-scale ALS gene discovery efforts.

Vitamin C is a very popular supplement in people living with ALS, perhaps due to its antioxidant mechanism, low cost, and low risk. Here we review the data on Vitamin C in ALS in hopes of helping patients make more informed decisions about it.

Melatonin is a naturally occurring hormone, and it is commonly taken as a supplement to induce sleep. Here we review some surprising mechanisms, pre-clinical data and case reports supporting its potential as an ALS treatment.

Light therapy has surprisingly plausible mechanisms through which it could influence the progression of ALS. Here we describe these, as well as some limited pre-clinical and clinical data, and information about dosing, risks, and costs.

Ketogenic diets, resulting in the formation of ketone bodies, have long been used to promote weight loss and to treat refractory epilepsy. Here we summarize the available data on ketogenic diets as a treatment for ALS.

Dr. Michael Benatar is the Walter Bradley Chair in ALS Research, a Professor of Neurology at the University of Miami Miller School of Medicine and the Principal Investigator of the CReATe Consortium. In this interview, he will discuss the CReATe Consortium's recent paper titled "Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS". The interview highlights the specific ways in which validated biomarkers could benefit therapeutic development for ALS.

Dr. Corey McMillan is an Associate Professor of Neurology at the University of Pennsylvania and this interview will be discussing his recent paper titled “Machine learning suggests polygenic risk for cognitive dysfunction in amyotrophic lateral sclerosis (ALS)” which discusses the contribution of genetics to heterogeneity we observe in ALS.

Dr. Benjamin Murdock is a Research Assistant Professor of Neurology at the University of Michigan and this interview will be discussing his recent paper titled “NK Cells associated with ALS in a sex- and age-dependent manner” which further expands his ongoing research examining the impact of sex and age on immune mechanisms in ALS.

Tamoxifen is an FDA approved estrogen receptor modulator that is currently prescribed to treat breast cancer. Here we review surprising evidence that it could someday be an ALS treatment, including its mechanisms of action, pre-clinical data, cases, trials and risks.

Spirulina, or blue green algae, is a supplement that is claimed to have antioxidant and anti-inflammatory properties. Here we review the problems we found with the single relevant preclinical ALS study, and some surprising real and potential risks associated with this product.

Lutimax is a supplement containing Luteolin, a flavonoid that has antioxidant, anti-inflammatory and neuroprotective mechanisms. Here we review case reports and a small trial claiming benefits in people with ALS.

Bee Venom contains substances that could plausibly affect the rate of ALS progression, and there are some positive (though flawed) preclinical studies and case reports associated with it. Since it has some potentially severe side effects and has not been tested in an ALS trial, our group advised against using it to try and slow ALS progression.

Vinpocetine is a prescription drug in many countries and is used to treat patients with stroke and memory loss (though meta-analyses have questioned its benefit in these populations). In the USA, it is sold as a nutritional supplement. Here we review the potential mechanisms, data from pre-clinical models, case reports, and a trial, and the safety of vinpocetine as an ALS treatment.

Apoaequorin (also called Prevagen) is a calcium binding protein first isolated from jellyfish. Here we review the theory and the single trial of this compound for treating ALS.

Azathioprine is an immunosuppressant drug. Here we review the mechanisms by which it could slow ALS progression, discuss the ALS reversals and the negative ALS trials associated with this drug, and highlight some of the serious side effects that can occur in patients taking it.

Accilion is a topical mineral cream. Here we discuss why we do not think it has a plausible mechanism of action for treating ALS. We also point out the problems interpreting the one anecdotal report of improvement in ALS symptoms associated with this treatment.

Vitamin E is one of the most popular, and most thoroughly studied, supplements in patients with ALS. Although it is inexpensive and safe, well designed trials have failed to find evidence that it can slow, stop, or reverse ALS progression. Interestingly, some data suggest that long term use of vitamin E might decrease a person's risk of getting ALS.

Vitamin E is one of the most popular, and most thoroughly studied, supplements in patients with ALS. Although it is inexpensive and safe, well designed trials have failed to find evidence that it can slow, stop, or reverse ALS progression. Interestingly, some data suggest that long term use of vitamin E might decrease a person's risk of getting ALS.

Leap2Bfit is a combination of many ingredients. The exact amount of each ingredient is not clear. While some of these products have plausible mechanisms and preclinical studies supporting their use in ALS, others do not. There are 3 "ALS reversals" associated with this product, but these may have different explanations. Several other patients under the care of ALSUntangled investigators have derived no clear benefit from this product. There can be serious risks associated with some of the ingredients in this product.

Leap2Bfit is a combination of many ingredients. The exact amount of each ingredient is not clear. While some of these products have plausible mechanisms and preclinical studies supporting their use in ALS, others do not. There are 3 "ALS reversals" associated with this product, but these may have different explanations. Several other patients under the care of ALSUntangled investigators have derived no clear benefit from this product. There can be serious risks associated with some of the ingredients in this product.

Ursodiol or ursodeoxycholic acid (UDCA) is a bile acid derivative of cholesterol. Since it can have antioxidant, anti-inflammatory and anti-apoptotic effects, it has mechanisms by which it could slow ALS progression. Here we discuss trials of UDCA in PALS, including the taurine-conjugated form (TUDCA). Some of these trials came out after our ALSUntangled review, and have changed our opinion about UDCA as an ALS treatment.

Ursodiol or ursodeoxycholic acid (UDCA) is a bile acid derivative of cholesterol. Since it can have antioxidant, anti-inflammatory and anti-apoptotic effects, it has mechanisms by which it could slow ALS progression. Here we discuss trials of UDCA in PALS, including the taurine-conjugated form (TUDCA). Some of these trials came out after our ALSUntangled review, and have changed our opinion about UDCA as an ALS treatment.

Propofol is an intravenous drug used for general anesthesia. Some people with ALS have reported benefits from this drug. Here we explore the rationale, the cases we found objective data on, and the serious risks of propofol as an ALS treatment.

Propofol is an intravenous drug used for general anesthesia. Some people with ALS have reported benefits from this drug. Here we explore the rationale, the cases we found objective data on, and the serious risks of propofol as an ALS treatment.

Carnitines are inexpensive, generally safe forms of amino acids. There are several mechanisms by which different carnitines might theoretically be helpful to a person with ALS. A flawed Italian trial suggested that acetyl-L-carnitine could slow ALS progression. Here we examine carnitines in more detail in hopes of helping patients with ALS make more informed decisions about them.

Carnitines are inexpensive, generally safe forms of amino acids. There are several mechanisms by which different carnitines might theoretically be helpful to a person with ALS. A flawed Italian trial suggested that acetyl-L-carnitine could slow ALS progression. Here we examine carnitines in more detail in hopes of helping patients with ALS make more informed decisions about them.

Gluten is a protein found in breads and cereals. In a small percentage of people, ingestion of gluten can trigger an autoimmune disease. Here we review the evidence that gluten-induced autoimmunity can mimic ALS, as well as the pros and cons of a gluten-free diet for people with ALS.