Using Stem Cells to Cure Autism, Epilepsy & Schizophrenia | Dr. Sergiu Pașca

Dr. Sergiu Pasca and Andrew Huberman delve into the intricacies of autism, a neurodevelopmental condition with a spectrum of expressions. Together they discuss the genetic roots, diverse manifestations, and the evolving understanding and treatment approaches.

Autism: A Complex Spectrum Condition

Autism Prevalence Nears 3%

Dr. Sergiu Pasca highlights the complexity of autism as a behaviorally defined spectrum resulting from neurodevelopmental disorders. He discusses with Andrew Huberman the notable increase in autism's prevalence, which has reached roughly 3% of the global population. Pasca elaborates on the puzzling rise from what was once a rare disease and considers the changes in diagnostic criteria over time.

Genetic Component Linked To Autism Forms

Autism: A Collection of Disorders With Diverse Genetic and Biological Roots

Pasca reveals that autism has a strong genetic component, which contrasts with the previously held psychoanalytic views of the '50s and '60s. He informs Huberman that when families come into the clinic with an autism diagnosis, there's a 20% chance of leaving with a genetic determination. Moreover, genetic mutations associated with autism could be inherited or result from de novo mutations, reflecting the disorder's genetic complexity.

Pasca points to hundreds of genes linked to specific forms of autism and indicates the condition's high heritability. The genetic variations are "individually rare but collectively common," and even historical environmental factors like [restricted term] are part of the wider picture. Autism, Pasca asserts, is not a single disease but a spectrum, where some people are fully functional while others are severely impaired.

Autistic Individuals: High-Functioning To Impaired Abilities

Debates on Autism Spectrum Symptom Differences and Treatment Approaches

Dr. Pasca is focusing on treatments for profound autism, emphasizing the diversity among autistic individuals, from high-functioning to those with considerable impairments. He addresses the skewed ...

The use of stem cells and organoid technology is revolutionizing our understanding of brain development and the modeling of neurological disorders.

Patient-Derived Ipscs Enable In Vitro Brain Development and Neurological Disorder Studies

Sergiu Pașca underscores the significance of pluripotent stem cells, which are essential in early embryonic stages, for their ability to differentiate into various organs. These cells allow researchers to model diseases and may eventually be used in transplants. Methods like the Yamanaka factors enable scientists to reprogram cells, essentially turning back the clock of a cell by removing age-related markers.

Ipscs Differentiate Into Neurons and Brain Cells, Enabling Observation of Neural Cell Development and Function

The reprogramming of these pluripotent stem cells allows for in-depth studies of neural cell development. Andrew Huberman discusses the use of iPSCs provided with Yamanaka factors to grow into neurons and other brain cells, which can be observed as they develop. Sergiu Pașca's lab has maintained human neuron cultures for up to three years, and these patient-derived neurons have been instrumental in observing conditions such as Timothy syndrome, where an excess of calcium was observed within the cells.

Organoids and Assembloids Model Brain Tissue and Circuit Self-Organization

These advanced in vitro models closely replicate developmental timings seen in the human brain, including neuronal maturation and the formation of functional neural networks.

Advanced In Vitro Models Mirror Human Brain Development, Neuronal Maturation Timing, and Functional Neural Networks Formation

Dr. Pașca describes the transition from 2D cultures to 3D self-organizing cells, inspired by Yoshiki Sasai's work, and reflects on the potential of these 3D models. The protocols developed allow for the growth of cell balls or organoids, which can self-organize into functional neural networks, demonstrated by the emergence of spontaneous activity. When’s team has even transplanted organoids into rat brains, where human cells integrated and responded to external stimuli, showing the possibilities of studying functional connections in real-time.

Organoids & Assembloids Enable Study of Brain Disorders, Capturing Emergent Properties Not Seen In 2d Cultures

Pașca emphasizes the importance of creating models that replicate true brain circuit properties, especially for understanding comple ...

Dr. Sergiu Pașca discusses the promising advancements in the treatment of profound autism and other severe neurological conditions using organoid and assembloid models derived from induced pluripotent stem cells (iPSC).

Ipsc Models Identify Genetic and Cellular Defects in Severe Autism and Neurological Conditions

In Vitro Study of Patient-Derived Neurons Reveals Insights Into Timothy Syndrome, a Genetic Autism Disorder

Dr. Pașca sheds light on Timothy syndrome, which is a genetic form of autism characterized by a single genetic mutation that leads to a relatively consistent presentation across affected individuals. By studying patient-derived neurons, researchers found a defect associated with calcium dynamics, offering concrete insights into this disorder. This knowledge could be key in understanding more complex disorders like autism. Discoveries made using iPSC orgainoid technology establish an advanced understanding of Timothy Syndrome, subsequently directing the development of nucleic acid-based therapies for the condition.

Gene Therapy Strategies Tested On Ipsc Models

Timothy Syndrome Insights From Ipsc Studies Enable Potential Autism Cure

Pașca highlights the comprehensive understanding gained from the in vitro studies of iPSC-derived neurons in patients with Timothy syndrome. This understanding has paved the way for the development of therapeutic strategies, potentially leading to a cure for autism.

Dr. Pașca conveys an optimistic outlook on focusing on genetic disorders and believes that by mastering one form, there is potential to extend those findings to treat other forms of disorders. He elaborates on gene therapy's development, pondering the preferred site in the brain to deliver the gene if it can't be delivered to the entire brain.

Pașca envisions using iPSC technology to recreate neurons from patients with severe autism, allowing for the study of complex brain circuits safely outside the body. This research offers vital insights into severe forms of autism, providing a base for developing effective treatments.

Assembloids For Modeling Neural Circuits in Epilepsy and Schizophrenia to Test Novel Therapies

While discussing organoid technology, Pașca points out its application in studying genetic forms of pain as well as its extrapolation to test gene therapy strategies for disorders, including epilepsy and schizophrenia. He emphasizes the use of this technology for disorders where individuals are severely impacted to the point where they cannot live independently or communicate effectively.

Pașca acknowledges the ...

Sergiu Pașca and Andrew Huberman delve deep into the ethical considerations around stem cell, organoid, and assembloid technology, touching on the importance of clear communication and collaboration in the scientific community to address potential ethical challenges.

Ethical Questions on Stem Cell and Organoid Integration Into Animal Models

Sergiu Pașca highlights concerns regarding the integration of human cells and organoids into animal models. These concerns center around consent for using human cells, the treatment of animals that receive transplants, and the potential emergence of sentience or enhanced abilities within the organoids. Pașca raises specific points on the source of embryonic stem cells, particularly their extraction from fertilized eggs after conception, which suggests potential ethical implications related to the timing of cell harvesting and use.

Timing of Transplantation and Integration Degree Critical for Ethical Implications

The degree of integration and the timing of transplantation are particularly critical for ethical implications. Pașca’s transplantation experiments show that if the transplantation is done too late, the cells do not integrate as well. Additionally, the developmental pace differences between species make integration challenging, as evidenced by the rapid development of a rat's cortex compared to human cortical cells.

In regards to the research of intractable forms of epilepsy, Pașca emphasizes that these ethical considerations, such as the timing and degree of integration when transplanting into live animal models, are vital. He addresses the importance of considering these factors, given the ethical impact of the substantial integration of human cells in the rat brain hemisphere.

Essential For Addressing Ethical Challenges: Clear Communication and Collaboration Among Scientists

Guidelines and Nomenclature for Responsible Scientific Use

Sergiu Pașca underlines the need for clear communication and collaboration among scientists to prevent misunderstandings regarding stem cell research. This need for collaboration is reflected in a paper published in Nature, detailing a framework for responsible scientific reporting and practice.

The conversation also touches on the importance of terminology for public understanding, with Pașca emphasizing the importance of accurate nomenclature, as terms such as "organoids" may suggest more complexity than these entities possess. A consortium is established for deciding on terms that sho ...