Using Stem Cells to Cure Autism, Epilepsy & Schizophrenia | Dr. Sergiu Pașca
Episode
143 min
Read time
2 min
Topics
Leadership, Psychology & Behavior, Science & Discovery
AI-Generated Summary
Key Takeaways
- ✓Autism prevalence and genetics: Autism now affects nearly 3% of the population, up from rare disease status decades ago. Twenty percent of patients receive genetic diagnosis identifying specific mutations. Males affected at 1:4 ratio compared to females, with strong heritability making it one of most genetic psychiatric disorders known.
- ✓Yamanaka factors breakthrough: Four genetic factors can reprogram adult skin cells into pluripotent stem cells without using embryonic tissue, eliminating ethical concerns. This 2006 discovery enables unlimited patient-specific neurons for disease modeling, taking months to generate but providing personalized cells for studying any neurological condition in laboratory settings.
- ✓Organoid developmental timing: Brain organoids grown in dishes follow intrinsic developmental timelines matching human gestation, switching from prenatal to postnatal molecular signatures at nine months without external cues. Cultures maintained for 600-800 days continue maturing, with myelination progressing into third decade, revealing cells possess internal developmental clocks independent of environmental factors.
- ✓Assembloid circuit formation: Four-part assembloids recreate sensory pathways by combining skin sensory neurons, spinal cord, thalamus, and cortex organoids in correct spatial order. Parts must be positioned properly or cells fail to connect. Within weeks, spontaneous synchronized activity emerges across entire pathway, enabling testing of pain medications and genetic pain disorders.
- ✓Timothy syndrome modeling: Single calcium channel mutation causing profound autism, epilepsy, and cardiac issues shows measurably prolonged calcium signaling in patient-derived neurons. This represents first genetic form of autism with clear biological mechanism, enabling development of targeted therapies through assembloid testing without animal models, with clinical trials now in preparation.
What It Covers
Dr. Sergiu Pașca explains how induced pluripotent stem cells enable creation of brain organoids and assembloids to study autism, schizophrenia, and Timothy syndrome, revealing developmental mechanisms and potential gene therapies for profound neurological conditions without using embryonic tissue.
Key Questions Answered
- •Autism prevalence and genetics: Autism now affects nearly 3% of the population, up from rare disease status decades ago. Twenty percent of patients receive genetic diagnosis identifying specific mutations. Males affected at 1:4 ratio compared to females, with strong heritability making it one of most genetic psychiatric disorders known.
- •Yamanaka factors breakthrough: Four genetic factors can reprogram adult skin cells into pluripotent stem cells without using embryonic tissue, eliminating ethical concerns. This 2006 discovery enables unlimited patient-specific neurons for disease modeling, taking months to generate but providing personalized cells for studying any neurological condition in laboratory settings.
- •Organoid developmental timing: Brain organoids grown in dishes follow intrinsic developmental timelines matching human gestation, switching from prenatal to postnatal molecular signatures at nine months without external cues. Cultures maintained for 600-800 days continue maturing, with myelination progressing into third decade, revealing cells possess internal developmental clocks independent of environmental factors.
- •Assembloid circuit formation: Four-part assembloids recreate sensory pathways by combining skin sensory neurons, spinal cord, thalamus, and cortex organoids in correct spatial order. Parts must be positioned properly or cells fail to connect. Within weeks, spontaneous synchronized activity emerges across entire pathway, enabling testing of pain medications and genetic pain disorders.
- •Timothy syndrome modeling: Single calcium channel mutation causing profound autism, epilepsy, and cardiac issues shows measurably prolonged calcium signaling in patient-derived neurons. This represents first genetic form of autism with clear biological mechanism, enabling development of targeted therapies through assembloid testing without animal models, with clinical trials now in preparation.
Notable Moment
Pașca describes the accidental discovery that organoid cultures survived far longer than expected when lab members revealed keeping cultures for 500-800 days during a cost-cutting meeting. This serendipitous finding led to breakthrough research showing human brain cells maintain intrinsic developmental timers for years in laboratory conditions.
Episode Transcript
Welcome to the Huberman Lab Podcast, where we discuss science and science based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is doctor Serju Posca. Doctor Serju Posca is a professor of psychiatry and behavioral sciences, and the director of the Stanford Brain Organogenesis Program. During today's episode, we discuss autism, schizophrenia, and human brain development generally. Both brain development during pregnancy, as well as during childhood, and leading all the way up to our third decade of life. During today's discussion, you will get the most up to date information about autism and its treatments. You'll learn why the prevalence of autism is rising, the role that genes play in autism, and the novel treatments that doctor Posca is developing to treat what is called profound autism, which are the most severe cases of autism. Doctor Posca is one of a small handful of researchers that pioneered the discovery and development of what are called organoids and assembloids, which are essentially human brain circuits derived from stem cells that form in a dish so that one can study them directly. And while that might sound artificial, today he explains why those organoids and assembloids are immensely powerful for understanding exactly what is wrong in psychiatric illnesses like profound autism, schizophrenia, and other psychiatric challenges, and for developing cures. So today, you're going to learn a lot about human brain development and about stem cells, which is going to be important for anyone interested in how the brain wires up, how to treat various diseases of the brain, but also for anyone who is considering stem cell therapies. As you'll soon learn, Sergio is an extraordinary scientist, but also an extraordinary teacher. By the end of today's episode, you'll have the latest information on stem cells, organoids, autism, and what is being done to cure autism and other psychiatric conditions. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with doctor Sergiu Posca. Doctor Sergiu Posca. Welcome. Thank you. It's great to be here. We're old friends. Shared a laboratory space years ago. We'll get back to that a little later. In the meantime, these days, there's a ton of interest and I think misunderstanding about autism. As soon as the topic of autism comes up, immediately, some people will say, why are we trying to cure this thing? I know autistic, children and adults that are delightful people that lead functional lives. They might be a little bit different or a lot different than other people, but why are we trying to quote, unquote cure autism? And then other people will say, …
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