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.
Podcast: Genetic therapies in store for neurodevelopmental disorders
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.
Brain imaging studies of infants with autism have shown a faster rate of expansion of a layer of the brain called the cortex in those who go on to be diagnosed with autism. Some infants also exhibit macrocephaly (larger than expected overall brain size). However, little is known about these features in autism. This study will develop a new model system utilizing organoids, which are aggregates of cells obtained directly from individual study participants and then further manipulated in a dish to recreate the cortex. In this way, scientists can understand how cells divide, expand, and grow. This researcher will then compare features in the organoids with brain scans collected from the same individual. This work will provide the research community with a novel way to test therapies and interventions on those with macrocephaly.
Most of the genetic research conducted to understand rare genetic forms of autism has been focused on the coding regions of the DNA. In genetics, the coding regions are specific parts of the DNA sequence that directly encode instructions for building proteins. There is still a lack of knowledge around the non-coding regions of the genome, which do not contain instructions to make proteins but rather regulate how genes are turned on and off. Recent studies have shown that the non-coding regions play an integral role in brain development. This study will look at over 700,000 non-coding variants in autism to determine their role and importance.
Following the initial analysis, regions that are determined to play a role in the coding of a gene called SCN2A will be targeted. SCN2A is a protein that controls how cells turn on and off, and is strongly tied to both autism and epilepsy. Identifying and validating the enhancers of ASD-associated genes like SCN2A will help scientists better understand mechanisms behind genetic influence of autism and comorbid features, and will also provide novel therapeutic targets for single gene disorders.
This project is graciously co-funded by FamilieSCN2A, the patient advocacy group that supports families with this genetic variation.
Compared to people without autism, the risk of Alzheimer’s disease is 2.6 times higher in people with autism, and they are twice as likely to die prematurely – with autistic women being at even higher risk for premature death. However, very few research studies focus on or even include autistic adults who are middle aged and older. This project capitalizes on a cohort of older autistic and neurotypical adults who receive assessments of brain structure, memory function, and intellectual ability at multiple timepoints as they age. Integrating brain imaging, genomic techniques, and statistical tools, this researcher will determine if autism risk genes also lead to memory decline and how these genes affect brain structure and the cortical thinning that is typical in all older adults. In addition, they will examine sex differences in autistic adult memory and changes in the memory system across age, with the goal of identifying sex-specific biomarkers that can be used to predict who will be most vulnerable to adverse aging outcomes. This work has implications for the future development of precision medicine and other interventions that will increase the quality of life for older adults across the spectrum.
On this week’s podcast episode, more on genetics as an influence to an autism diagnosis with a twist: can genetics lead to a specific treatment for core symptoms – across the board? How do you measure such broad symptoms? Our Rett Syndrome family friends and colleagues developed a novel outcome measure to capture what was most important to them, and the FDA approved it for use in a clinical trial. Years later, a new drug was approved that led to a reduction in behaviors associated with Rett Syndrome. Autism can take a lesson from this. In addition, can the genetics of autism be explained by parents with similar phenotypes? This is called assortative mating. The answer is complex.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450502/pdf/fped-11-1229553.pdf
Very rarely are scientists able to look at single genes within the brains of people across neuropsychiatric disorders and understand how the genes in each of these cells influence expression of proteins and interactions of different cells with each other. Recently, a collaboration called PsychENCODE released a series of papers that investigated what genes are expressed in what cells in autism in different situations, how cells that communicate interact with more support or glial cells, and what mechanisms are in place to identify ways in which the broad environment (chemicals, contextual factors, illness) may influence gene expression leading to disorders like autism, schizophrenia and bipolar disorder. This podcast summarizes these papers as they are related to autism – or at least tries to.
In recognition of Father’s Day on the 16th, today’s podcast includes the latest research on fathers. Fathers may often be the “secondary caregiver” but should hardly be dismissed as inconsequential. Father’s sensitivity and insightfulness plays an important part in development, psychiatric diagnoses (including autism) change the the chance of having a child with autism, and more understanding is being done on the heritable factors associated with chemical exposures in the father.
https://www.tandfonline.com/doi/full/10.1080/14616734.2024.2326416
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11059471/pdf/main.pdf