Dr. Jerry Silver: Trailblazing Spinal Cord Research

About this video

• Video Title: Dr. Jerry Silver: Trailblazing Spinal Cord Research
• Channel: Guy Kawasaki’s Remarkable People
• Speakers: Guy Kawasaki, Dr. Jerry Silver
• Duration: 01:16:40

Overview

This video features an interview with Dr. Jerry Silver, a neuroscientist specializing in spinal cord injury research. Dr. Silver discusses the progress of his work, from foundational discoveries in developmental biology to the current clinical trials of a peptide-based treatment (NVG291) aimed at promoting nerve regeneration after spinal cord injury. He explains the science behind the treatment, its historical development, the challenges faced, and the potential implications for patients.

Key takeaways

• Phase 1B 2A Trial of NVG291: The trial signifies a major milestone, moving from animal models to human patients with spinal cord injuries, indicating the drug's safety and potential efficacy.
• Mechanism of Action: The NVG291 peptide works by blocking inhibitory molecules (proteoglycans) in scar tissue that prevent nerve regeneration, and by blocking a specific receptor (PTP Sigma) on damaged nerve fibers.
• Treatment Administration: The peptide is administered subcutaneously (under the skin), typically in the stomach, and travels to the spinal cord and brain without direct injection into the central nervous system.
• Historical Research Roots: Dr. Silver's work originated from studying nerve fiber guidance in the developing eye, identifying barrier molecules (proteoglycans) that prevent nerves from growing in the wrong direction, a concept he later applied to spinal cord injury.
• Challenges and Persistence: Dr. Silver faced significant skepticism and funding challenges for his unconventional ideas about proteoglycans in the brain and their role in inhibiting regeneration.
• Importance of Chronic Injury Research: Contrary to common practice, studying chronic spinal cord injuries (long after the initial event) yielded better results, suggesting that regeneration is possible even in long-standing conditions.
• The Role of Glia and Scars: Glial cells in the brain and spinal cord form scars that act as barriers, and while protective initially, they impede nerve regeneration. Dr. Silver's work aims to dismantle these barriers.
• Company Formation and Licensing: The development led to the formation of the biotech company NerveG, which is now conducting clinical trials for NVG291, after overcoming setbacks with larger pharmaceutical companies.
• The "Fortunate Accident": A student's forgotten rats in the lab, studied 18 months after injury, provided crucial evidence that chronic injuries could still show significant recovery with the treatment.

The drug was initially in partnership with GlaxoSmithKline (GSK).

The partnership with GSK failed because:

• Spinal cord injury was considered a small market by GSK's upper management, who prioritized larger markets with higher profit potential.
• GSK preferred to focus on conditions like Alzheimer's disease or Multiple Sclerosis, which had millions of patients compared to the approximately 16,000 new spinal cord injuries per year in the US.
• At that time, Dr. Silver's research was primarily focused on acute injuries, not the chronic injuries that later showed more promising results.

The video transcript mentions AbbVie in relation to the drug's development.

Here's what the transcript says about AbbVie:

• After the deal with GSK fell through, GSK suggested AbbVie as a potential partner.
• AbbVie became interested in licensing the peptide and conducting clinical trials.
• Dr. Silver and his team spent another year doing experiments for AbbVie.
• AbbVie appointed a special team to the project.
• However, AbbVie also ultimately decided against proceeding because they viewed spinal cord injury as too small a market. They wanted Dr. Silver's team to have already conducted research on Multiple Sclerosis (MS), which they hadn't done extensively at that point (though they later found the peptide had positive effects in MS models).
• AbbVie's decision led to the project being "killed," leaving Dr. Silver and his team without a partner at that time.

The transcript does not mention Eli Lilly.

Yes, Adcon L did work for its intended purpose. It was used successfully in patients to prevent scar tissue formation around nerves, significantly reducing pain and improving outcomes in cases of nerve entrapment and after spinal surgeries. One of the first US patients, Mr. Smith, experienced relief from severe pain after multiple failed surgeries when treated with Adcon L. The product was used in hundreds of thousands of operations worldwide.

However, the company, Gatech, eventually failed and fell apart. According to Dr. Silver, this was due to:

• Greed and selfishness among some of the company's management.
• These individuals ruined the product and its potential due to their focus on personal gain.
• This led to FDA issues (the FDA "blackballed" them) and ultimately the company going broke.