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Little Brains Answer Big Questions

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This week we talk to Sergiu Pasca from Stanford University. He has revolutionized the field of understanding the field of brain development in neurodevelopmental disorders and just published a new study which examined the genetic influence of brain assembly. The way he does this is quite remarkable. His lab uses assembloids, which are many many many stem cells which form into a tiny brain. He explains what an interneuron is, why it is important for brain function, and how genetics can influence how these neurons work. This way the development of the brain from the first cell can be tracked and even manipulated to understand what happens in autism, and what therapies might be the most helpful to target these interneurons. Thank you Dr. Pasca.

Open access! https://pubmed.ncbi.nlm.nih.gov/37758944/

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The earliest differences across ASDs

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New neurons can be generated in a dish (amazing in itself), and then these neurons can then be studied to examine how they grow, expand, divide and connect. Using this technology, researchers are finding differences in several cell functions in different forms of autism. These differences are in proliferation, which is an increase in the number of cells, as well as the ability of those cells to signal to each other once they are formed. Some autism brains have too many cells, others do not proliferate as quickly as typical developing cells. These things are somewhat dependent on the genetic background which controls head size.

While these different forms of autism all have differences in proliferation, sometimes in different directions, they are all altered, regardless of the genes involved. So, is this one basic biological features that may help identify autism from the earliest points in development? Since they can be studied at any time in life, is this a new biomarker? Should they be used to better understand different subgroups? Much needs to be studied but please listen to this week’s ASF podcast with Dr. Robert Connacher to learn more about the studies going on at Rutgers University to examine this issue.

https://www.sciencedirect.com/science/article/pii/S2213671122002089

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Families work hard for treatments

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Unfortunately, families hear more about what does work to help families with ASD rather than what does not work. But through the course of decades of research, scientific projects and hours of families participation, there is a better picture of what treatments are, and are not, helpful. This week’s podcast will review what drugs have shown to not be effective so far in treating restrictive and repetitive behaviors and also provides an update on umbilical cord blood stem cell transfusions on social communication behaviors.

https://www.jpeds.com/article/S0022-3476(20)30334-6/pdf

https://jaacap.org/article/S0890-8567(20)30265-3/pdf

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Oops the media did it again…

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Last week CNN.com reported on a study that showed slight improvement of autism symptoms in children that received a single infusion of their own umbilical cord blood.  While the study was interesting, the authors were the first to acknowledge the limitations, however, this did not stop the media from misrepresenting the results.  Details are explained in this podcast.  In addition, a big win this week for precision or personalized medicine:  different symptoms and different genetic mutations are linked to different outcomes from different anti-seizure medications.

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Exploiting genetics to understand environmental risks for autism

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On March 13th, Dr. Mark Zylka from UNC gave a 60 minute overview of how researchers are using autism-relevant genetic mutations in cells to start to understand the interactions between genetics and thousands of environmental factors on gene expression.  He pointed out the convergence of pathways in how genes and these environmental factors worked in the brain, and they included:  neuroinflammation, early brain development, turning neurons on and off, and cell signaling.  Dr. Valerie Hu from George Washington University commented on the important impact of these results and perspective from her lab studying epigenetically modified genes, like RORA, which also may be sensitive to common chemicals found in our environment.  The entire webinar, including the questions that they were able to answer from participants, is found here.

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IGF-1 might be the next big thing in autism treatment

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This week’s podcast summarizes a new neural stem cell study and a recent review article on IGF-1 treatment in developmental disorders. IGF stands for Insulin Growth Factor and is essential for generation of new neurons, and shaping and health of existing neurons.  Patients with autism spectrum disorder are already starting to be treated with IGF-1, and now there is even more evidence validating it as a target.  If you are interested in participating in a research trial at Mt. Sinai School of Medicine using IGF-1, call the Seaver Center at  212-241-0961.