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Episode
Curing Autism, Epilepsy & Schizophrenia with Stem Cells | Dr. Sergiu Pașca
~180 min
Episode Brief·YouTube

Curing Autism, Epilepsy & Schizophrenia with Stem Cells | Dr. Sergiu Pașca

Andrew Huberman
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TL;DR

The four things you'd lose by not watching

4 items

TL;DR

The four things you'd lose by not watching

4 items
1

Dr. Sergiu Pașca explains that autism is a spectrum of behaviorally defined conditions, with profound autism (severe, often with intellectual disability and epilepsy) having strong genetic drivers. Prevalence is ~3% and rising, partly due to diagnostic changes.

2

His lab pioneered organoids (3D self-organizing brain-region cultures) and assembloids (fused organoids forming circuits) from induced pluripotent stem cells (iPS cells), avoiding ethical issues of embryonic stem cells. These recapitulate human brain development timing, including a postnatal NMDA receptor subunit switch at 9 months in a dish.

3

The work has led to a molecular therapy for Timothy syndrome (a single-gene autism/epilepsy form): an antisense oligonucleotide that corrects calcium channel splicing, developed entirely using human stem cell models without animal models. First-in-human clinical trial is being prepared.

4

Key ethical challenges include ensuring proper consent, avoiding trivializing terminology like 'mini-brains', and assessing emergent properties when transplanting human organoids into animals. The human cells integrate best when transplanted into early postnatal rat cortex, growing 6-8x larger than in vitro and revealing hidden disease phenotypes.

Recommendations

Products, supplements, and tools mentioned in the episode

1 item

Walking as a daily practice (Pașca's personal habit)

Practice

When asked how he maintains his fitness and energy, Pașca mentioned he walks a lot, often over 12,000–15,000 steps per day. He walks to and from work, and especially when traveling, exploring museums. He said art is his only other pursuit besides science.

Pașca's walking habit emerged from necessity during medical school in Romania, where he had no time for traditional exercise due to combining clinical work and research. He walked between experiments and often walked at night discussing science with students. At Stanford, he continues the habit, walking between buildings and at night. He credits this with sustaining his high energy and creativity over decades. He did not frame this as a universal health recommendation but as his personal sustainable practice.

Personal experience

I walk all the time, I like to walk, especially when I travel... I walk a lot in museums. I think you could probably trace where I've done most of the walking, and it's probably done in museums, or in California, walking at night, and discussing science with students or others.

I do more than 12,000-15,000, for sure. Yeah, and I walk all the time, I like to walk.

Find Walking

Notable quotes

Lines worth pulling out — contrarian, specific, or perfectly phrased

2 items
You've demystified the psychiatric disease. ... you went all the way down to a molecular defect, a point mutation, figure out the rest. And now you're on a verge of potentially, perhaps not reversing, but at least improving some.
Lubert Stryer's powerful encapsulation of the significance of developing a therapy from a genetic form of autism: connecting behavioral symptoms to a single molecular defect and a potential fix. It marks a turning point for psychiatry.
The human brain builds itself, right? Of course, there are instructions, but there's no blueprint. There's no plan that the brain constantly looks to make sure that it actually made all the connections properly, right? Instructions are sort of revealed at every step, for kind of like the next step, and it mostly comes from the cells, finding each other.
A beautiful description of developmental self-organization, challenging the common misconception of a detailed genetic blueprint.

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Topics covered

autismstem-cellsinduced-pluripotent-stem-cellsyamanaka-factorsorganoidsassembloidstimothy-syndromecalcium-channelsschizophreniacrisprgene-therapybrain-developmentmyelinationneurodevelopmental-disordersepilepsypain-pathwaystransplantationethicsnomenclaturevaccines-autism-myth
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Educational summary of the cited expert source — not medical advice. Open the source recording linked above and consult a qualified physician before acting on any protocol.