Podcasts about developmental neurobiology

Ana Faro is an Equality, Diversity & Inclusion (EDI), Culture and Workplace Wellbeing specialist, with over 15 years of experience in the Higher Education sector and with the commitment to create positive social impact. She joins Jo on this podcast to talk about mental health and her work as a specialist in Diversity, Equality, & Inclusion (DEI). Ana studied Molecular Biology & Genetics at University of Lisbon, Portugal, and has a PhD in Stem Cell Biology & Cancer from Utrecht University, The Netherlands. In 2010, Ana moved to the UK to pursue her postdoctoral studies in Developmental Neurobiology, at University College London. Throughout her career as a scientist, Ana was always committed to creating opportunities for students from underrepresented and disadvantaged backgrounds to access experience and gain insight into a career in academia. A few years ago, Ana left the bench and followed her passion for EDI to carve a new career path where she supports Academic institutions in building inclusive workplace cultures with a focus on equity of experiences, belongingness, mental health and wellbeing. Find more podcast episodes here: ⁠⁠⁠⁠⁠⁠https://access2perspectives.pubpub.org/podcast⁠⁠⁠ Host:⁠⁠⁠⁠⁠⁠ Dr Jo Havemann⁠⁠⁠⁠⁠⁠, ORCID iD ⁠⁠⁠⁠⁠⁠0000-0002-6157-1494 ⁠⁠⁠⁠⁠⁠Editing: ⁠⁠⁠⁠⁠⁠Ebuka Ezeike⁠⁠⁠⁠⁠⁠ Music:⁠⁠⁠⁠⁠⁠ Alex Lustig⁠⁠⁠⁠⁠⁠, produced by⁠⁠⁠⁠⁠⁠ Kitty Kat ⁠⁠⁠⁠⁠⁠License:⁠⁠⁠⁠⁠⁠ Attribution 4.0 International (CC BY 4.0)   ⁠⁠⁠⁠⁠⁠ At Access 2 Perspectives, we guide you in your complete research workflow toward state-of-the-art research practices and in full compliance with funding and publishing requirements. Leverage your research projects to higher efficiency and increased collaboration opportunities while fostering your explorative spirit and joy. Website: ⁠⁠⁠⁠⁠⁠https://access2perspectives.pubpub.org⁠⁠⁠⁠ --- Send in a voice message: https://podcasters.spotify.com/pod/show/access2perspectives/message

Nick talks to Dr. Sergiu Pasca, a developmental neuroscientist and professor at Stanford University. They discuss topics related to human brain development, the origins of neuropsychiatric disease like autism & schizophrenia, new technologies for studying brain development, stem cells, and recent experiments from Dr. Pasca'a lab utilizing brain "organoids," "assembloids," and human-animal transplantations.SUPPORT M&M:Sign up for the free weekly Mind & Matter newsletter:[https://mindandmatter.substack.com/?sort=top]Learn how you can further support the podcast: [https://mindandmatter.substack.com/p/how-to-support-mind-and-matter]Support the show

Dr Claire Novorol trained as a Specialist Registrar in London before completing a PhD in Developmental Neurobiology at the University of Cambridge. With 18 months left until becoming a Consultant, she left Medicine to co-found Ada Health — an AI powered self-assessment health tool. Ada has raised $190 million dollars to date with over 10 million users. We speak about her decision to leave Medicine when she did, whether the NHS is where startups go to die and the power of timing and just taking a calculated risk when it makes sense for you. You can find me on Twitter @MustafaSultan and subscribe to my newsletter on www.musty.io

Dr. Leigh Peterson, Ph.D., Vice President of Product Development at United Therapeutics discusses data published in the "New England Journal of Medicine" (Jan 2021) on the INCREASE study evaluating Tyvaso in pulmonary hypertension associated with interstitial lung disease (PH-ILD). The INCREASE study is the first to demonstrate a clear benefit in patients with PH-ILD, a life-threatening disease with no currently FDA-approved treatments. She talks about what's next for Tyvaso as they look to achieve FDA approval. Leigh Peterson: In her role as Vice President, Product Development, Dr. Peterson is responsible for coordinating and managing all aspects of preclinical and clinical development of United Therapeutics’ products. Dr. Peterson joined United Therapeutics in 2008 as a Senior Clinical Research Scientist and was promoted to her current role as Vice President of Product Development in March 2017. Dr. Peterson received a BS in Biochemistry from the University of Wyoming, a PhD in Molecular Biology - Human Genetics from the University of Utah, and conducted postdoctoral research in Developmental Neurobiology at The Rockefeller University.

What are some of the affordances we can leverage to engage English learners in STEM classes in remote and hybrid learning environments? How might we make synchronous meetings more engaging to promote growth in content area knowledge, language skills and collaborative work? What are some tools and strategies we can use to incorporate effective visuals, manipulatives and other supports in remote environments? We discuss these questions and much more in our conversation with Dr. Stephen Fleenor. Stephen is a scientist-turned-educator who is inspired by the principles of sheltered instruction and growth mindset, particularly in the service of English learners. In 2014, Stephen earned his PhD in Developmental Neurobiology and sought to empower the next generation of thinkers as a high school science teacher at a Title I school in San Antonio. He has developed innovative approaches to working with ELs and economically disadvantaged students, and has presented his ideas across various districts, as well as at regional conferences. A central component of Stephen’s pedagogy is student ownership of personal growth throughout the school year. This approach has been particularly effective in promoting language and content acquisition for ELLs, and under his leadership his department closed the gap in EL performance on the State of Texas Assessments of Academic Readiness (STAAR) in Science. In 2017, Stephen was awarded the Edgewood ISD District Teacher of the Year Award and the KENS5 ExCEL Award, and went on to serve as a science instructional coach for Edgewood ISD. In addition to his PhD from Oxford, Stephen holds an M.Ed. in School Leadership from the University of the Incarnate Word and a B.S. in Biology from the University of Texas at Austin. Stephen lives in San Antonio with his wife, a fellow educator. You can learn more about the work Stephen is doing by visiting Seidlitz Education's Upcoming Events page. Also, check out his new Visual Non-Glossary website here. Finally, please consider leaving us a review on Apple Podcasts or wherever you get your podcasts. This will help us continue bringing you the best topics and guests on Highest Aspirations. --- Send in a voice message: https://anchor.fm/highest-aspirations/message

Teresa Purzner is a neurosurgeon, developmental neurobiologist, and the founder and CSO of Cerebelly, a company dedicated to providing organic, farm-fresh baby food to nurture and promote infant brain development. As a mother of three and a doctor in Developmental Neurobiology, Teresa knows the importance of providing our children with the nutritious food they need for their developing brains and growing bodies. After the birth of her first child and feeling disappointed in the baby foods that were on the store shelves, Teresa and her brother Nick decided to team up with world-class experts in pediatrics, nutrition, and food science to create farm-fresh, organic baby food that truly promotes healthy brain development. Teresa joins me today to share what inspired her to start Cerebelly and discuss the connection between the foods we feed our children and healthy brain development. She shares how she founded her company, the steps she took to learn about starting a business, and the importance of taking baby steps to overcome seemingly insurmountable obstacles. We also discuss the biggest challenge she has faced while building the Cerebelly brand, how she overcame that challenge, and how she balances building a business, working in the OR, and raising three young children.   “It seems like an impossible task to create a company when you have absolutely no background in business, but just tackle one problem at a time. There is no ‘one problem’ that is insurmountable.” - Teresa Purzner Today on When She Founded: How her fascination with the brain and neurobiology began and what led her to start Cerebelly The science behind the connection between nutrition and healthy infant brain development How she turned her idea for the Cerebelly baby food products into a reality The steps she took to learn about starting a business The importance of taking baby steps to overcome challenges and obstacles The biggest problem Teresa has faced in her business and how she overcame it How she balances her career with raising three children The driving force behind Cerebelly Teresa’s advice to female founders     Connect with Dr. Teresa Purzner:   Cerebelly Facebook Twitter Instagram LinkedIn         Subscribe, Rate & Share Your Favorite Episodes!   Thanks for tuning into today’s episode of When She Founded with your host, Somer Hamrick. If you enjoyed this episode, please head over to Apple Podcasts to subscribe and leave a rating and review.   Don’t forget to visit our website, connect with Somer on LinkedIn, and share your favorite episodes across social media.

Why are advanced STEM classes a good fit for many English learners? What strategies can teachers leverage to maximize impact on diverse learners in STEM classes? How might we remove barriers that prevent many English learners from taking advanced classes throughout their academic careers? We discuss these questions and much more in our conversation with Dr. Stephen Fleenor. Stephen is a scientist-turned-educator who is inspired by the principles of sheltered instruction and growth mindset, particularly in the service of English learners. In 2014, Stephen earned his PhD in Developmental Neurobiology and sought to empower the next generation of thinkers as a high school science teacher at a Title I school in San Antonio. He has developed innovative approaches to working with ELs and economically disadvantaged students, and has presented his ideas across various districts, as well as at regional conferences. A central component of Stephen’s pedagogy is student ownership of personal growth throughout the school year. This approach has been particularly effective in promoting language and content acquisition for ELLs, and under his leadership his department closed the gap in EL performance on the State of Texas Assessments of Academic Readiness (STAAR) in Science. In 2017, Stephen was awarded the Edgewood ISD District Teacher of the Year Award and the KENS5 ExCEL Award, and went on to serve as a science instructional coach for Edgewood ISD. In addition to his PhD from Oxford, Stephen holds an M.Ed. in School Leadership from the University of the Incarnate Word and a B.S. in Biology from the University of Texas at Austin. Stephen lives in San Antonio with his wife, a fellow educator. --- Send in a voice message: https://anchor.fm/highest-aspirations/message

Dr. Jonathan Delafield-Butt, Director of the cross-disciplinary Laboratory for Innovation in Autism and Reader in Child Development at the University of Strathclyde, discusses his interesting research in early cognitive development.   Fascinated by psychology, Delafield-Butt's work studies the genesis of conscious experience as well as the deep emotional foundations of general psychological development, with a special focus on the motor disruption seen in autism spectrum disorder. Delafield-Butt earned a Ph.D. in Developmental Neurobiology from the University of Edinburgh Medical School and completed his postdoctoral work while attending the Universities of Edinburgh and Copenhagen. He is a contributing writer to the notable book titled, The Infant Mind: Origins of the Social Brain.   Dr. Jonathan Delafield-Butt talks about his background and the reasons why he was so motivated to study the infant mind and infant development. As he states, he was interested in the mind, and he thought it best to start at the beginning, to understand the human mind in its early development. As he explains, his early work was in the field of chemistry, then he moved into neuroscience to get a better understanding of the structure, composition, and origins of the human mind. Delafield-Butt talks about how he wanted to truly pinpoint the emergence of consciousness and the development of the human agency. By studying movement, Delafield-Butt was seeking to ascertain exactly when movement is first organized with an awareness, conscious actions.    The Ph.D. provides an overview of the stages of development, and how awareness and conscious actions are developed, and progress. He discusses participatory awareness and the moments that infants begin to demonstrate their conscious awareness. He cites important studies and the historical work of other scientists working with consciousness theories, going back to the early 1950s. And he provides an overview of newer data that discusses cortex and brain stem theories. As he states, all of our experiences are taking place through the brain stem, and that the brain stem does have associative memory. Ultimately, Delafield-Butt states that some areas of the brain are more to the foreground than others, depending upon the given need at the time. He discusses various layers, memories, and associations—incorporating instinct, problem-solving, etc. Delafield-Butt states that while infants do not have the same conceptual organization, an abstraction of ideas, or the mastery of language, they are in fact as conscious as adults.     Dr. Jonathan Delafield-Butt is a respected member of the World Association for Infant Mental Health and the International Society for Autism Research. He is also an affiliate member of the Gillberg Neuropsychiatry Centre at the University of Gothenburg. 

Can investigating how the neocortex is built further our understanding of the function of the brain? Join Michael and Andre as they sit down with Dr. Oscar Marin, Director and Group Leader at the Centre for Developmental Neurobiology at Kings College London to discuss how the brain is built. In a wide-ranging conversation, they explore the components that come together to build the brain, how programmed cell death may contribute to the normal development of the brain, the contribution of developmental disorders to psychiatric disorders, and adult neurogenesis.

Is there an elixir Batman can take to reduce the effects of head trauma after a fight with Bane? Find out on this week's episode of School of Batman! Our guest this week is Chris Wynder, who has a PhD in Developmental Neurobiology from Rockefeller University. You can find Chris on Twitter: https://twitter.com/cw_infogardener. __________________ Impact Moderato by Kevin MacLeod is licensed under a Creative Commons Attribution license (creativecommons.org/licenses/by/4.0/) Source: incompetech.com/music/royalty-fre…isrc=USUAN1100618 Artist: incompetech.com/ Cool Vibes - Film Noire by Kevin MacLeod is licensed under a Creative Commons Attribution license (creativecommons.org/licenses/by/4.0/) Source: incompetech.com/music/royalty-fre…isrc=USUAN1100863 Artist: incompetech.com/ Mechanolith by Kevin MacLeod is licensed under a Creative Commons Attribution license (creativecommons.org/licenses/by/4.0/) Source: incompetech.com/music/royalty-fre…isrc=USUAN1100879 Artist: incompetech.com/

Repairing the damaged brain is the one of the holy grails of neuroscience. On this episode, Grace and Melissa sit down with Dr. Freda Miller, a Senior Scientist at the Hospital for Sick Children, who firmly believes that studying the developing brain can give us insights into how to rebuild it in circumstances of damage or degeneration. Dr. Miller is a Canada Research Chair in Developmental Neurobiology, a Fellow of the Royal Society of Canada, and a Howard Hughes Medical Institute International Research Scholar. She discusses her transition from biochemistry to neuroscience, gives advice to budding scientists, and explains why she engages in science communication. She also talks about how her research has finally led her to several clinical trials in children with brain injury. Our hosts also catch up with Dr. Donald Mabbott, Clinical Psychologist and Neuroscientist, to discuss how some of Dr. Miller's findings with a drug called metformin resulted in a pilot clinical trial for children with acquired brain injury after cancer treatment.

Repairing the damaged brain is the one of the holy grails of neuroscience. On this episode, Grace and Melissa sit down with Dr. Freda Miller, a Senior Scientist at the Hospital for Sick Children, who firmly believes that studying the developing brain can give us insights into how to rebuild it in circumstances of damage or degeneration. Dr. Miller is a Canada Research Chair in Developmental Neurobiology, a Fellow of the Royal Society of Canada, and a Howard Hughes Medical Institute International Research Scholar. She discusses her transition from biochemistry to neuroscience, gives advice to budding scientists, and explains why she engages in science communication. She also talks about how her research has finally led her to several clinical trials in children with brain injury. Our hosts also catch up with Dr. Donald Mabbott, Clinical Psychologist and Neuroscientist, to discuss how some of Dr. Miller's findings with a drug called metformin resulted in a pilot clinical trial for children with acquired brain injury after cancer treatment.

[intro music]   Host – Dan Keller Hello, and welcome to Episode Thirty-Seven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Jeanne Loring, who works with human induced pluripotent stem cells in a mouse model of MS. But to begin, we’d like to tell you about one of the most useful features of the MS Discovery Forum.   Each week somewhere between 30 and 110 papers related to multiple sclerosis are published in the scientific literature. At MSDF, we endeavor to list them all, publishing links to a curated set of each week’s new papers every Friday at msdiscovery.org/papers.   The first step in curating this list is an automated PubMed query that pulls all papers containing the terms multiple sclerosis, myelin, optic neuritis, acute disseminated encephalomyelitis, neuromyelitis optica, transverse myelitis, experimental autoimmune encephalomyelitis, cuprizone, neurodegeneration, microglia, and several related terms. This query returns many false positives. MSDF editors read all the titles and most of the abstracts and make judgments about which papers are directly relevant to MS or related disorders. Last week, for example, the query returned 139 papers and, in our judgment, only 58 of them – 42% – were truly MS-related. Some weeks the proportion is even lower than that.   The query terms neurodegeneration, myelin, and microglia are responsible for most of the false positives. Neurodegeneration, in particular, returns many references related to other neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and hypoxia, to name a few. Editorial judgments on which articles are relevant are often subjective, and we frequently struggle with those decisions. It’s easy to decide relevance when an article actually mentions multiple sclerosis. It’s harder when it mentions only myelin or only Th17 cells. If you think we’ve missed an important MS-related article—or if you think we’ve included an irrelevant article—I hope you’ll let us know by emailing us at editor@msdiscovery.org. And we’re open to suggestions on how to adjust our PubMed query to decrease false positives and false negatives.   Once we’ve chosen which of the articles to include in the week’s list, we select between two and four of them as Editors’ Picks. Those are the week’s articles that seem to us to be the most important or interesting or intriguing. Once again, we invite readers to take issue with our choices. We’d love to hear about important articles that we have not designated Editors’ Picks or, on the contrary, Editors’ Picks that don’t deserve the honor.   [transition music]   Now to the interview. Dr. Jeanne Loring is Professor of Developmental Neurobiology and Director of the Center for Regenerative Medicine at the Scripps Research Institute in San Diego. She and her collaborators have been testing human neural precursor cells derived from embryonic stem cells in a mouse model of MS. The cells are injected into the spinal cords of immunocompetent mice with a model of MS induced by a neurotropic hepatitis virus. The cells are rejected within a week, but in that time they suppress the immune system and induce remyelination.   Interviewer – Dan Keller In terms of how you came upon your most recent finding about human pluripotent stem cells in the mouse model of MS, could you give me a little bit of the back story?   Interviewee – Jeanne Loring Oh yeah, sure. It was really interesting. So Tom Lane and I set out to try to develop a stem cell therapy for MS using human cells. So as a control experiment, we took human pluripotent stem cells, in this case embryonic stem cells, and turned them into neural precursors; differentiated them just a little bit. And then we transplanted them into Tom’s mouse model of MS. These mice were not immunosuppressed, and so we expected the cells to be rejected. And this was just our first experiment. But the results were not what we expected. After the cells were rejected, the mice started getting better, and their clinical scores improved. And then after several months, these mice were almost indistinguishable from normal mice.   The first thing we thought was that we’d gotten the cages mixed up, and we were looking at something different. But we’ve repeated the experiment now more than a hundred times, and about 75% of the time we get the same result. So what this tells us is that these cells that we put into the animals are having some effect during the seven days that they exist in the animals that leads to both immunosuppression and remyelination and a clinical improvement which is quite remarkable.   MSDF When you say 75% of the time, does that mean you get almost no effect 25 % of the time? Or does it mean that 75% or the mice? Because that would say whether you’re making your stem cells right or not.   Dr. Loring It’s 75% of the mice.   MSDF How do you explain it at this point, or where do you go from here to find a way to explain it?   Dr. Loring So once we’d realized that we had a phenomenon that was repeatable, we realized that there was something special about these cells. And we tested other cell types, like the pluripotent stem cells that they were derived from, and human fibroblasts, and discovered that neither one of those was effective. And since then we’ve also tried other ways of making neural precursor cells, and those cells aren’t effective either. So it’s something extremely special about the cells that we used in these experiments, which is very lucky when you think about it.   So we’ve now, both Tom and I – even though we’re not in the same place – we’ve set out to try to find out what it is about these cells that gives them these properties. Our first sort of cut on this – our hypothesis – is that the cells are secreting something that has a lasting effect. Our sort of big picture idea is that there are probably more than one protein or glycoprotein being secreted. And together they suppress the immune system so they act on the inflammatory response so that they increase the number of regulatory T cells that are produced and decrease the other T cell types. And they induce remyelination.   So Tom is now working on trying to identify what factors these cells make that are inducing the T regulatory cells. And on my side, we’re trying to identify what it is that makes them remyelinate.   MSDF When you make these cells, how do you know you got a good batch? Can you characterize them? Are there biomarkers, and you can say, “We did it right this time?”   Dr. Loring Yes. In fact, that turns out to be really important because we did it wrong a few times. And we have a gene expression signature. It’s essentially diagnostic assay for this particular cell type. We’ve boiled it down to a set of qRT-PCR markers. And, because we have collaborators in Australia, we had to be able to transfer this quality control assay to them. So far it seems like those markers, I think it’s a group of 10 or 12 markers, seem to be predictive of the cells’ working in the animals.   MSDF And just to clarify, that’s real time quantitative polymerase chain reaction? How are you going about characterizing what they’re doing? I mean, are you doing cytokine measurements or you’re looking at cells that get produced in the mice?   Dr. Loring Tom is really handling the cells that get produced in the mouse. He’s doing the T cell analysis. What we’re doing, we developed an in vitro cell culture method to look for the effect of these cells on maturing oligodendroglia in culture. And we found that something secreted by these cells which shows up in their culture medium actually induces maturation of oligos – of OPCs – in vitro. I guess that’s another result that we didn’t expect to be quite so clear. So that shows that there’s something that is secreted by the cells. I mean, that’s the most likely idea. And on Tom’s side, he’s shown that the conditioned medium from the cells induces T-reg generation. And on our side, we’ve shown that conditioned medium from the cells induces oligo maturation.   So now we’re trying to figure out what it is in that conditioned medium because now we think we can do a cell-free therapy for MS if we can identify what the factors are. It would be much simpler for us to do even a protein therapy for MS than it is to do a cell therapy. So both sides are taking sort of a candidate gene approach in which we’re identifying the proteins that are most highly specifically expressed in the cells that work in the mice. We have a list of those proteins, and we’ve sort of snatched a few candidates out of that group, and we’re testing to see whether each one of those proteins in purified form has the same effect as the conditioned medium.   The other approach, which is more tedious but more likely to actually tell us what’s going on is for us to fractionate the medium into different sized proteins and then test each one of those fractions. We’re in the process of doing that right now.   MSDF But it sounds like these cells are pluripotent. Not pluripotent in the normal sense of a stem cell leading to different lineages, but they have a couple of effects. One is the immunomodulatory, the other is regenerating oligodendrocytes. Do you think it really requires the gamish of proteins? If you fractionate them, will you possibly lose the signal? And that’s a big matrix to put back together again.   Dr. Loring Yes, it is. And obviously, if we get no signal from our fractions, we’ll put our fractions back together again and try to find out whether – there are only three fractions, really, right now. So we’ll try different combinations of these fractions to try to find out if we can reproduce the effect. The effect is quite robust. We essentially get no maturation in medium conditioned by other cell types, but we get very strong maturation when we use conditioned medium from this particular neural precursor cell.   MSDF If you only have three fractions now, is it because you just have chosen not to fractionate it even more until you know what’s going on?   Dr. Loring Yes, we’re trying to hone in on it. So we don’t want too many different things to look at right away. I’m hoping that we find that only one of those fractions works, and that we can discover everything is within that fraction, but I really can’t predict what’s going to happen.   MSDF It sounds like the approach would be to put everything in except one each time as opposed to keep adding back. You’ve got to find the one critical one missing that makes the thing not work.   Dr. Loring Yes, and eventually we will do that with specific antibodies, but right now that is, since we don’t really have our candidates narrowed down enough, that isn’t a viable approach. But you’re absolutely right. We want to find out if that’s missing, whatever the things that are that are missing. And I’m hoping it’s not so complex that it’s five or six or seven proteins, because that’ll make it much harder for us.   MSDF How do characterize the condition of the mice?   Dr. Loring So that’s Tom’s area of expertise. It’s essentially an observation of the mice over time. We have a movie which I can show you, but I can’t actually do it in a recording. It’s quite obvious when the mice – they’re blind scored so the person who looks at the mice and sees how well they’re walking around doesn’t know whether they’re controls or experimentals. If you just see the movies that are selected at particular times after the cells have been transplanted, it’s quite dramatic. They have a much better clinical score. Essentially, they’re almost normal after six months.   MSDF And how are you sure that the cells you injected into the spinal cord are gone, that they’ve been rejected completely?   Dr. Loring That’s a good question. We used a method for live imaging of cells in which we use luciferase to label the cells. And then we used an instrument which allows us to image the cells in mice – in living mice – over time. So we did this in individual mice and saw that they disappeared over time. And after eight days we couldn’t detect them anymore. That doesn’t mean there isn’t one or two left because the resolution isn’t that high. We will go back eventually and look through sections of the spinal cords and see whether we can detect any. The other thing we can do is (skip 13:37) a human-specific markers. So we can just take a section of the spinal cord and find out if there’s any human cells in it at all, or any human genes in it at all. But we haven’t done that yet.   MSDF Do the cells have to be gone? Have you tried injecting a second time?   Dr. Loring No, we haven’t. We don’t know. We really don’t know. It would be very interesting if it reversed the effects. Then we’d really have a problem to solve.   MSDF What else is there important to add or that we’ve missed that’s important to this kind of research?   Dr. Loring So our dream is that we will identify a group of proteins and the concentration of those proteins necessary to have these two effects in this mouse model. And then we will do some biological engineering. We’ll be putting the cells into these little spheres and matrix that allows slow release of these proteins or controlled release of these proteins. And then, instead of putting cells in, we’ll put these beads in. And I don’t know whether that would end up being the final product or not, but there are lots of ways to deliver proteins, and this one I find rather attractive because it doesn’t require pumps or syringes. And I think that’s certainly the direction we’re going to try to go in. And so Tom Lane and I have just gotten an NIH grant for five years of funding, which seems like a very long time to me. So in five years we will have discovered the best way to deliver these things. We’ll discover what they are and the best way to deliver them. Tom has put conditioned medium into the mice, and it also works.   MSDF Because I was going to ask, had you encapsulated the cells just to see that the supernatant does it without cell contact?   Dr. Loring It turns out that the conditioned medium itself, you inject that into spinal cord, it’s not as dramatic an effect, but you have a clear clinical improvement.   MSDF Have you tried injecting it either IV or intraperitoneally?   Dr. Loring Yes. Well, we didn’t inject the conditioned medium. We did try injecting the cells, and they pretty much stayed where we injected them. These cells, unlike mesenchymal stem cells, they aren’t very migratory. So they don’t really have the receptors that cause them to move to areas of inflammation like CXCR4, for example; they don’t express that on their surfaces. So that does not seem to be a good delivery method for these cells. They don’t go anywhere.   MSDF I was also thinking that if something they secrete is important, whether it circulates. Maybe they’re not making enough concentration if you inject them outside of the central nervous system, but it seems like you’re going to be faced with a little cumbersome problem in a clinical situation years and years ahead from now if you have to keep injecting proteins into the spinal cord as opposed to more peripheral.   Dr. Loring I agree. And the solution to that is generally to look for peripheral effects and then try to suppress those when you do a therapy like this. That’s a long time, and we could certainly imagine how we would do it. But we need to know what those proteins are before we can decide on whether we expect them to have effects peripherally or not. But I agree with you; delivering them intravenously would be far easier.   MSDF I know you have a lot of work ahead of you now with this, but is there another animal model of MS – or even another mouse model of MS – where you can see if it works even in a mouse model different from this one?   Dr. Loring Yes, we’re actively pursuing that with our collaborators in Australia. And it’s interesting because they’ve gotten some positive preliminary results using the EAE model, but the approach to the EAE model I’ve realized is quite different. Generally, what people do is they provide the therapy at the time that the pathology is developing, and they try to prevent it, which is a really different idea than what we had using the mice that are already paralyzed. So they have found that if you can deliver the cells at least close to the spinal cord, then you can see some effects. The problem is that in Australia, and this is one of those technical things we had not anticipated, they don’t have permission to inject cells into the spinal cord. So they have to go through their animal rights people or their animal protection groups and try to get permission to do so. So with Craig Walsh at UC Irvine we have started doing parallel experiments with the EAE model. I’m not necessarily sure that it’s going to have similar effects. I mean, I really don’t know.   MSDF Can you describe how these mice in your experiments were made to have MS?   Dr. Loring Yes, they were given a virus, a neurotropic virus, which kills off the oligodendroglia. They become demyelinated, and there is a secondary inflammatory response. So the mice are actually paralyzed in their hind quarters at least by the time we put the cells in. They have to be fed by hand. So this is not a trivial thing to do. But we’re trying to reproduce the effects during the progressive form of MS, for example, or during an attack of MS. So we’re trying to repair the mice or cure the mice that are in a condition which would be similar to the worst case scenario for people with MS.   MSDF Do you think this may also have effects not only on the myelin, but also on damaged neurons?   Dr. Loring We don’t know, because the mice haven’t really had enough time to get a lot of neuronal damage, but that’s a very good question. We don’t know yet.   MSDF I appreciate it. Thank you.   Dr. Loring You’re welcome. It was a pleasure.   [transition music]   Thank you for listening to Episode Thirty-Seven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]

Pain experienced by the very young and very old and the similar issues arising when dealing with these very different types of patient. This edition has been funded by the Big Lottery Fund’s Awards for All Programme in Northern Ireland. In this edition of Airing Pain, Paul Evans speaks to experts from Belfast and London about the similarities, differences and challenges in treating pain in infants and the elderly. Maria Fitzgerald, Professor of Developmental Neurobiology at University College London, mentions the outdated theory that babies do not experience pain and how this misconception has been disproved. She raises the issue of communication, perhaps the biggest problem with babies and the elderly (particularly those with dementia) - if they cannot communicate about their pain effectively, their pain often cannot be adequately addressed. She also discusses the scientific research she and her team are carrying out as well as the importance of treating pain at an early age. Paul speaks to Dr Pamela Bell, Chair of the Pain Alliance of Northern Ireland and former Lead Clinician for Pain Services at the Belfast Trust. She discusses how pain treatments work for infants and the consequences of not managing pain during the early stages of their development. Peter Passmore, Professor of Aging and Geriatric Medicine at Queen’s University Belfast, talks to us about the large number of dementia patients who are thought to live with pain and the need for medical staff and carers to be able to recognise changes in the patients’ behaviour and therefore become more able to address their pain. Contributors: * Maria Fitzgerald, Professor of Developmental Neurobiology at University College London * Dr Pamela Bell, Chair of the Pain Alliance of Northern Ireland and former Lead Clinician for Pain Services at the Belfast Trust * Peter Passmore, Professor of Aging and Geriatric Medicine at Queen’s University Belfast First broadcast 21.05.13 #Dementia #Postsurgicalpain #Brainimaging #Carers #Childrenandyoungpeopleinpain #Communicationskills #Explainingyourconditiontoothers #Facialexpressionsasameasureofpain #Medication #Olderpeople #Opioids #Patientperspective #Psychologicalapproachestopainmanagement #Research #Sleep #Talkingtoyourdoctor #Youngpeopleandchildren

Guest: Allan Schore, MD, PhD Host: Laura Humphrey, PhD Dr. Allan Schore, a member of the clinical faculty of the Department of Psychiatry and Biobehavioral Sciences at UCLA David Geffen School of Medicine and at the UCLA Center for Culture, Brain and Development discusses early relationships and experiences from a neurobiological perspective.

Guest: Allan Schore, MD, PhD Host: Laura Humphrey, PhD Dr. Allan Schore, a member of the clinical faculty of the Department of Psychiatry and Biobehavioral Sciences at UCLA David Geffen School of Medicine and at the UCLA Center for Culture, Brain and Development discusses the stages of brain development from infancy through adolescence.