Unlocking the Brain's Mysteries with Stem Cells and Organoids

Cells and Organoids Source: Excerpts from "Using Stem Cells to Cure Autism, Epilepsy & Schizophrenia | Dr. Sergiu Pașca" on the Huberman Lab podcast. I. Introduction: The Enigma of Brain Disorders and a Novel Approach This briefing summarizes a discussion with Dr. Sergiu Pașca, a professor of psychiatry and behavioral sciences and director of the Stanford Brain Organogenesis Program. Dr. Pașca is a pioneer in the development of organoids and assemblids—human brain circuits derived from stem cells grown in a dish—to study and potentially cure psychiatric and neurological conditions like profound autism, epilepsy, and schizophrenia. The conversation highlights the complexities of these disorders, the historical challenges in studying the human brain, and the revolutionary potential of stem cell-derived models for developing targeted therapies. II. Key Themes & Most Important Ideas/Facts 1. Understanding Autism: A Complex Spectrum Behaviorally Defined: Autism is a "complex condition" and a "spectrum," primarily defined by observing behavior, "there's no biomarker." This behavioral definition is common for most psychiatric disorders, leading to a "disconnect with the biology." Rising Prevalence: The prevalence of autism has significantly increased, now affecting "close to almost 3% of the general population." This is a notable rise from when it was considered a "rare disease" decades ago. Historical Misconceptions: Early theories (1950s-60s) included the "refrigerator mother hypothesis," attributing autism to emotionally cold parenting. Strong Genetic Component: Twin studies in the 1970s first indicated a "strong heritable component." In the last 10-15 years, "hundreds of genes" have been identified, which when mutated, are "strongly associated with specific forms of autism," particularly "profound autism." Profound vs. Functional Autism: The spectrum includes individuals with "autistic traits that are fully functional" and "kids that have autism who are very impaired and will require actually lifelong care." Profound autism often co-occurs with intellectual disability and epilepsy. Not One Disease: "Autism is not one disease." Dr. Pașca compares it to "fever of the 19th century in medicine"—a symptom with various underlying biological causes requiring different treatments. Gender Disparity: Autism is more prevalent in males, with a ratio of 1:4 (females to males). Possible reasons include diagnostic biases (girls may be better at "masking the symptoms") and inherent differences in male and female brain development and resilience to injury. Unproven Theories: While various factors like the microbiome, diet, and even fever have been anecdotally associated with autism, "most of the evidence points out towards a very strong genetic component." There is "no solid evidence that vaccines cause autism." Genetics and Location of Origin: Many associated genes are "expressed in the periphery," suggesting that "perturbing some of these critical periods of development can have certainly devastating effects later on," even if the initial impact is outside the central nervous system. Current Treatment Landscape: For profound autism, there is "no single treatment." About 20% of patients receive a "genetic diagnosis," but "sadly that doesn't do that much today because we don't really have specific therapies for those forms." The remaining cases are "idiopathic." Source:    • Curing Autism, Epilepsy & Schizophrenia wi...