Podcast: A lesson on leucovorin

Two pediatricians, a child neurologist and a child psychiatrist walk into the ASF weekly science podcast to discuss the safety, efficacy and appropriateness of leucovorin, the drug that the HHS is fast tracking through the FDA approval process. Does it work? Is it safe? What should I do or know when I talk to my doctor?

Here is a link to the statement by the Society of Developmental and Behavioral Pediatrics: https://sdbp.org/sdbp-statements-regarding-leucovorin-tylenol-and-autism/

Here are the four studies mentioned:

Here is a requested correction to one of the papers where a calculation error was made:

https://pubpeer.com/publications/987569A781B9A602DCE7358D4513A0

The National Institutes of Health just awarded $50million to 13 different research sites to better understand genetic and environmental contributions to an autism diagnosis, or increase in prevalence in autism, as well as environmental factors which improve the quality of life for children and adults with ASD.

You can read about them here or listen to this 30 minute podcast which summarizes them.

https://dpcpsi.nih.gov/autism-data-science-initiative/funded-research

In an effort to better understand the causes of autism in those with a known genetic variant associated with ASD or other developmental disorders, in 2010, the Simons Foundation launched Simons VIP, now known as  Simons Searchlight – an online international research program studying nearly 200 rare genetic neurodevelopmental disorders and working with over 60 patient advocacy groups across these conditions. 

Since its inception, it has grown to not just study specific genes, but to provide de-identified aggregate data to researchers & industry, support for patient advocacy groups to bring together families & researchers (thanks to the generosity of the Simons Foundation), identify even more genes associated with autism, and create international communities. 

These communities share similar underlying mechanisms even though there are sixty genes represented within Simons Searchlight. This week’s podcast episode is a conversation with the principal investigator of Simons Searchlight, Dr. Wendy Chung, talks about why genes associated with autism and other neurodevelopmental disorders are so important to study, what the scientific community has learned, and how Patient Advocacy Groups have grown and flourished as a result of this understanding.

This week the @WSJ reported that the upcoming MAHA report will include acetaminophen (also known as Tylenol in the United States, although it is used all over the world) use during pregnancy as a cause of autism. Acetaminophen is used in about 7.5 % of pregnant women. This is one of many environmental exposures that had previously been investigated in association with an autism diagnosis, but then disproven following rigorous and large scale studies with the right design. For example, is it acetaminophen or fever during pregnancy? Is it acetaminophen or some sort of underlying genetic susceptibility? This week’s ASF podcast episode explores the association and what pregnant women should know.

https://pubmed.ncbi.nlm.nih.gov/40804730

https://pubmed.ncbi.nlm.nih.gov/40898607

https://pubmed.ncbi.nlm.nih.gov/39982125

https://pubmed.ncbi.nlm.nih.gov/38592388

As the autistic brain ages, is it more vulnerable to other brain disorders? Recent scientific discoveries in Parkinson’s Disease and Alzheimer’s Disease show that there may be an underlying mechanism between these diseases and autism. However diagnosing someone with autism with an additional brain disorder, especially dementia, can be difficult. This week’s podcast covers the increased risk of Parkinson’s Disease in autism, as well as provides advice from a group of experts on how to diagnose an autistic person with dementia, since there may be overlap in features.

https://jamanetwork.com/journals/jamaneurology/fullarticle/2834684?guestAccessKey=4961ce0b-24e8-412a-b1cc-35fc5826fbe1&utm_source=fbpage&utm_medium=social_jamaneur&utm_term=17468134139&utm_campaign=article_alert&linkId=837634061

https://pmc.ncbi.nlm.nih.gov/articles/PMC12144002

This week’s ASF weekly science podcast episode features Dr. David Amaral, who directs the Autism BrainNet. The Autism BrainNet is a program that organizes the collection of post-mortem brain tissue and then distributes it to autism researchers worldwide to better understand the brains of people with autism. He discusses major scientific discoveries about the mechanisms of autism in the brain that were only possible by using this resource, and the brave generosity of families that make the program happen. Anyone can register to learn more about new scientific research and the program itself, it’s important that everyone at least know the program exists for future planning. You can learn more here: www.autismbrainnet.org.

Gene therapies have been in the news lately. They are being used to help individuals who have a genetic variant linked to a disorder or disease, including but not limited to: spinal muscular atrophy, carbamoyl phosphate synthetase 1 (CPS1) deficiency, diabetes and some types of cancers. What is the promise in rare genetic forms of neurodevelopmental disorders and autism? On this week’s podcast episode, scientists from Jaguar Therapeutics discuss their ongoing studies in Phelan-McDermid Syndrome and how gene therapies hold promise for treating neurological impairments caused by a known genetic variant. The interview provides basic information of what a gene therapy is, how it works, how it is used and what is monitored during these treatments.

https://www.nih.gov/news-events/news-releases/infant-rare-incurable-disease-first-successfully-receive-personalized-gene-therapy-treatment

This year’s International Society of Autism Research Meeting was filled with great presentations about causes, diagnosis, interventions, mechanisms, supports, understanding sex differences and different populations of those with autism. But not everyone could fly to Seattle to attend. This week’s podcast episode provides a short summary of just some of the science presented. Michael Lombardo provided a keynote that included data from his research included on this podcast: https://blubrry.com/asfpodcast/137452290/factors-that-influence-heterogeity-and-how/

If you would like a copy of the INSAR program book, email me at ahalladay@autismsciencefoundation.org. Sorry, it’s too large to attach in the summary!

There is a cell in the brain called the microglia which has been traditionally overlooked as a target for therapies. New research supported by ASF and @FraxAresearch suggests that altering the function of microglia in the brain may help support the development of healthy and functional connections in the brain that may be impaired in autism, making the microglia a prime candidate for research. In this podcast episode, Drs. Marine Krzisch from @UniversityofLeeds and Dr. Mike Tranfaglia at @FraxAResearch describe the approach and how it can be developed to create specific therapies, that when combined with behavioral interventions, can drastically alter someone’s abilities. Dr. Krzisch is also interviewing families about how the findings will be explained when they are ready, what is important to them and what should research emphasize in the future. Participants will be compensated, just email her: M.Krzisch@leeds.ac.uk

It happens every year – this one belonged in the 2024 year end highlights but was published late in the year. Researchers at UCSD, UCLA and CHLA followed families with autism whose genetic test revealed a rare variant. Did it make a difference in care? Understanding? Referrals? Listen to this week’s podcast episode to learn all about it. If you are in need of a genetic test, here are some things to know: https://www.alliancegenda.org/genetic-testing

Reference here: https://www.sciencedirect.com/science/article/pii/S1098360024002673

Animal models of autism, including cell based models, have received criticism because autism is a uniquely human condition so there is no value in studying it in a model like a mouse or a cell. On the other hand, model systems have been used for decades to develop therapies for a myraid of other conditions and disorders, and produced evidence-based treatments for not just autism but conditions from ADHD to schizophrenia. So why is there so much backlash about this line of research? The ASF podcast talks to Jill Silverman at UC Davis to get some perspective.

https://pubmed.ncbi.nlm.nih.gov/35285132

https://www.vox.com/future-perfect/377739/autism-research-mice-lab-models

This project will expand an existing longitudinal study that tracked children from infancy and recently reported that a high proportion of those who were later diagnosed with autism showed an excess volume of cerebrospinal fluid in their brains when they were 6 months old. To date, assessment of these infants stopped at a diagnosis. This student will administer additional assessments to these families to determine whether this increase in cerebrospinal fluid persists as the children age, whether it’s associated with any behavioral features including attention difficulties, executive function and ADHD, and whether it predicts differences in autism severity.