Noah Davidsohn - "The Science of Rejuvenation: Practical Pathways to Reverse Aging"

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Introduction to Dr. Noah Davidson

  • Dr. Noah Davidson, the speaker, earned his PhD in bioengineering from MIT and completed a post-doctoral fellowship at Harvard in George Church’s lab, focusing on gene therapy and aging.
  • He is the Chief Scientific Officer and co-founder of Rejuvenate Bio, a biotechnology company that emerged from Harvard and Church’s lab.
  • Davidson expresses excitement about translating longevity science into therapeutics aimed at making people younger and healthier.

Societal Crisis of Aging

  • Davidson highlights a societal crisis concerning aging, where spending on individuals aged 65 and older exceeds spending on those under 18 by a trillion dollars.
  • Despite representing only 35% of the population, older adults account for 50% of healthcare expenditures, primarily due to chronic age-related diseases.
  • He critiques the healthcare system for its focus on treating individual diseases rather than addressing the underlying issue of aging itself, referring to it as “sick care” rather than healthcare.
  • Davidson underscores the need for therapeutics that target aging, which is the highest risk factor for developing chronic diseases.
  • He notes a positive trend in increased investment in longevity science, which may lead to beneficial developments in the near future.

Outline of Presentation

  • Davidson outlines his talk, which will cover two platform technologies developed by Rejuvenate Bio aimed at addressing the complex problem of aging.
  • He mentions plans to enter the veterinary market and highlights existing corporate partnerships in that sector.
  • Lastly, he discusses the challenge of bringing a generalized therapy to market, which requires targeting specific age-related diseases for clinical trials.

Team at Rejuvenate Bio

  • Davidson introduces his co-founder, Dan Oliver, who has a background in MBA and is passionate about translating science into practical therapeutics.
  • Their partnership began during Davidson’s post-doctoral work, where he transitioned from a traditional academic career to entrepreneurship.
  • Davidson mentions his dog, Bear, as the inspiration for starting Rejuvenate, emphasizing the relevance of veterinary applications in their research.
  • He acknowledges the contributions of George Church and Dr. Katherine Hy, both influential figures in gene therapy and aging research, who support their mission.

Therapeutic Goals

  • The primary goal of Rejuvenate Bio is to utilize gene therapy to target aging directly and treat multiple age-related diseases.
  • Davidson emphasizes the need for permanent solutions to chronic problems like aging and age-related diseases.
  • He mentions the necessity of creative clinical strategies and business models to tackle the complex issue of aging therapeutics.

Longevity Associated Genes

  • Davidson introduces the first platform technology focused on longevity-associated genes, which are derived from research showing which genes extend lifespan in mice.
  • The therapeutic aims to treat various age-related diseases and enhance healthspan, having demonstrated effectiveness in multiple conditions such as heart failure, diabetes, and obesity.
  • He references a seminal paper he published during his post-doctoral fellowship that highlighted the therapeutic potential of specific gene combinations.
  • The combination of anti-TGF-beta1 and FGF-21 was shown to effectively treat multiple age-related diseases, including kidney failure.

Epigenetic Reprogramming

  • Davidson discusses the second platform technology centered on epigenetic reprogramming, which has shown potential to double the remaining lifespan of elderly mice.
  • This technology can significantly extend lifespan even in mice with pre-existing health issues, demonstrating its potential impact on aging therapies.
  • Collaborations with other labs have shown that epigenetic reprogramming can improve visual acuity and regenerate nerves in mice.
  • Davidson explains the challenges of translating this technology to humans, particularly the complexity of using multiple viruses for gene delivery.
  • To address these challenges, they developed an inducible system that can deliver multiple genes within a single AAV, enhancing safety and effectiveness.

Clinical Applications

  • Davidson outlines their approach to targeting specific diseases such as ALS and FSHD through the reprogramming technology, which aims to restore youthful characteristics to aging cells.
  • He emphasizes the importance of developing therapies that can address the needs of older patients, rather than targeting younger populations.
  • The veterinary market is a significant focus, with ongoing clinical studies in pets demonstrating the effectiveness of their therapies.

Veterinary Market Initiatives

  • Davidson highlights the prevalence of mitral valve disease in dogs, which affects about 7% of the canine population, indicating a substantial market for their therapeutic interventions.
  • Rejuvenate Bio has established multiple partnerships with leading animal health companies to develop and commercialize their therapies.
  • A long-term study has shown that their therapy can delay disease progression in pets by one to two years, demonstrating significant clinical benefits.
  • Davidson expresses enthusiasm about upcoming partnerships and the potential for their therapies to be brought to market within the next couple of years.

Human Therapeutic Development

  • For human therapeutics, Rejuvenate Bio is focusing on FGF-21, which has shown promise in treating chronic diseases and is well-studied for its safety and efficacy.
  • FGF-21 has demonstrated the ability to improve various health parameters, including cardiac health, metabolic function, and immune response.
  • Davidson discusses the therapeutic’s potential to address arrhythmias and other cardiac conditions, emphasizing its advantages over traditional gene replacement strategies.
  • The company aims to target specific cardiac diseases as part of their strategy to expand their therapeutic applications beyond aging.

Future Directions and Market Potential

  • Davidson concludes by discussing the multi-billion dollar market potential for their therapies, particularly in gene therapy and metabolic health sectors.
  • He highlights the importance of targeting large patient populations to maximize the impact and accessibility of their treatments.
  • Davidson expresses optimism about the safety and efficacy of their therapies, which could facilitate regulatory approval and widespread adoption.

Q&A Session

  • During the Q&A, Davidson addresses questions regarding the effectiveness of their therapy on various arrhythmias and discusses observed side effects.
  • He notes that while the therapy has not been tested on all arrhythmias, it is expected to be effective for many due to its mechanism of action.
  • Davidson emphasizes the promising safety profile of FGF-21 gene therapy based on data from both animal studies and initial trials in pets.
  • He also discusses the potential for biologics to activate FGF-21 and the challenges associated with achieving therapeutic levels through such methods.
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