Ep. 291: “Functional Precision Medicine” Featuring Dr. Scott Younger
Apr 1, 2025
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Dr. Scott Younger, Director of Disease Gene Engineering at Children’s Mercy Hospital, dives into the world of functional precision medicine. He reveals how personalized antisense oligonucleotides can reverse disease phenotypes in organoid models of Duchenne muscular dystrophy. Younger emphasizes the importance of his lab's connections to the rare disease community, fostering collaboration with clinicians. The discussion highlights innovative approaches to personalized therapies, addressing the challenges of accessibility and costs in advanced healthcare.
Dr. Scott Young emphasizes the role of personalized antisense oligonucleotides in reversing disease phenotypes for Duchenne muscular dystrophy using organoid models.
The podcast discusses chronic stress affecting intestinal stem cells through the CA-DMV pathway, highlighting a direct neural link to gut health.
Research on liver regeneration reveals that manipulating gene expression in specific hepatocyte populations can enhance recovery, opening new therapeutic strategies.
Deep dives
Impact of Chronic Stress on Intestinal Stem Cells
Chronic stress negatively affects the function of intestinal stem cells, linking it to accelerated aging processes. Research demonstrates that the activation of the central amygdala dorsal motor nucleus of the vagus, referred to as the CA-DMV pathway, plays a significant role in this stress-induced impact. Findings show that this pathway influences intestinal stem cell functionality independent of microbiota interactions, suggesting a direct neural connection between stress and intestinal health. This intricate relationship underlines the complexity of the stress response in the body and calls for further investigation into potential therapeutic interventions.
Regeneration Mechanisms in Liver Function
The liver's regenerative capacity relies on the proliferation of hepatocytes, highlighting its unique role among organs. Research into distinct metabolic zones within the liver reveals how different hepatocyte populations respond to physiological demands and environmental insults. Key findings indicate that manipulating specific genes like URI1 can enhance liver regeneration by altering glutamate levels in hepatocytes, linking metabolic changes to regenerative responses. This connection between metabolism and liver functionality opens avenues for new therapeutic strategies aimed at enhancing liver restoration in patients.
Advancements in CRISPR Technology for Embryo Models
The utilization of CRISPR activation (CRISPR-A) allows the self-organization of mouse embryonic stem cells into embryonic models, resembling pre-gastrulation stages. By activating specific gene regulatory elements like GATA6 and CDX2 through CRISPR-A, the research demonstrates the potential for orchestrated cell movements and lineage specification in these embryo models. Such advancements in genome editing underscore the effectiveness of CRISPR-A in refining organoid technology to mimic natural embryonic development more closely. This progress represents a significant step forward in experimental embryology, pushing the boundaries of current model systems.
Patient-Derived Organoids for Precision Medicine
The development of patient-derived organoids offers innovative solutions for modeling rare diseases and personalizing treatment strategies. By generating these organoids from patient-specific induced pluripotent stem cells (iPSCs), researchers can recapitulate disease phenotypes in vitro, thus enabling tailored therapeutic approaches. Studies demonstrating the restoration of functionality in specific organoids highlight the potential of using personalized antisense oligonucleotides to correct disease-causing mutations effectively. This method showcases the transformative possibilities of individualized medicine, bridging the gap between research and clinical application.
Navigating the Challenges of Rare Disease Research
The landscape of rare disease research faces obstacles including financial constraints and regulatory hurdles in deploying personalized therapies. Efficient and scalable methods for producing patient-specific iPSCs are critical in addressing these challenges, as they significantly reduce costs and turnaround times for generating cellular models. Additionally, the integration of advanced AI technologies presents opportunities for improved data analysis and understanding of genetic variations associated with rare diseases. As the research community continues to collaborate across various institutions, the goal remains to provide effective, personalized treatment options for patients suffering from rare conditions.
Dr. Scott Younger is the Director of Disease Gene Engineering within the Genomic Medicine Center at Children’s Mercy Hospital. His research focuses on producing patient-derived cellular models to develop functional precision medicine. He talks about using personalized antisense oligonucleotides to reverse disease phenotypes in organoid models of Duchenne muscular dystrophy. He also discusses his lab’s personal connections to the rare disease community and the opportunities for collaborations with clinicians at Children’s Mercy. (36:52)
