Using Existing Drugs in New Ways to Treat & Cure Diseases of Brain & Body | Dr. David Fajgenbaum
Timestamps are as accurate as they can be but may be slightly off. We encourage you to listen to the full context.
Podcast Summary
This episode features Dr. David Fajgenbaum, an MD and professor at the University of Pennsylvania who shares his remarkable story of surviving a near-fatal diagnosis of Castleman's disease through drug repurposing. After being told multiple times by experts that there were no treatment options remaining, Dr. Fajgenbaum used his medical knowledge and relentless determination to discover that rapamycin (sirolimus), originally approved for organ transplant rejection, could treat his condition. (64:00)
- The episode explores how existing FDA-approved drugs can treat diseases other than what they were originally intended for, revealing a massive blind spot in modern medicine where life-saving treatments may already exist but go undiscovered.
Speakers
Dr. David Fajgenbaum
Dr. David Fajgenbaum is a professor of translational medicine and human genetics at the University of Pennsylvania. He's an MD-PhD who nearly died five times from Castleman's disease before discovering that rapamycin could treat his condition. He founded the nonprofit Every Cure, which uses AI to identify new uses for existing FDA-approved drugs across all diseases, and has already identified 14 successful drug repurposing opportunities that have saved lives.
Key Takeaways
Most Drugs Have Multiple Untapped Uses
The average FDA-approved drug can bind to 20-30 different proteins in the body, yet most are only approved for one or two specific conditions. (08:37) Dr. Fajgenbaum explains that 80% of the 4,000 FDA-approved drugs are already generic, meaning there's no financial incentive for companies to discover new uses. This creates a massive opportunity for drug repurposing that could help millions of patients with currently "untreatable" conditions. For example, aspirin isn't just a pain reliever—it also reduces heart attack risk and can lower colon cancer recurrence by 29% in patients with specific genetic mutations.
You Must Take Agency in Your Healthcare
Dr. Fajgenbaum emphasizes that patients cannot be passive participants in their healthcare, especially when facing serious illness. (18:47) His key recommendations include: connecting with disease-specific organizations that often know about treatments being used globally, identifying and consulting with world experts in your condition, and persistently asking questions about alternative treatments. When his doctor said "there's nothing more we can do," Fajgenbaum challenged this by noting they hadn't tried all 4,000 available drugs—leading to his life-saving discovery.
Build and Utilize Your Information Network
Having access to medical knowledge networks can dramatically impact health outcomes. (22:55) Dr. Fajgenbaum illustrates this with the heartbreaking example of DADA2, where children died from strokes for years while a life-saving TNF inhibitor treatment existed but wasn't widely known. The key is not just having medical connections, but knowing people who know the right people. This highlights the critical importance of disease advocacy groups and seeking multiple expert opinions rather than relying on a single physician's knowledge.
The "Hope-Action-Impact" Circuit Drives Success
Dr. Fajgenbaum describes a powerful psychological circuit that sustained him through his medical journey: hope drives action, action creates impact, and impact generates more hope. (67:18) This aligns with neuroscience research on the anterior mid-cingulate cortex, which is associated with tenacity and the will to lean into challenges. This circuit is particularly crucial when facing serious health challenges, as it prevents the paralysis that can come from overwhelming circumstances and maintains forward momentum toward solutions.
Systematic Drug Repurposing Can Save Lives
Rather than relying on random discoveries, systematic approaches to drug repurposing using AI and comprehensive databases can identify life-saving treatments. (24:04) Dr. Fajgenbaum's Every Cure nonprofit uses machine learning to analyze all drugs against all diseases, ranking potential matches by likelihood of success. This approach has already led to successful treatments like pembrolizumab for angiosarcoma, which went from a uniformly fatal cancer to having 18% of patients surviving beyond one year. The goal is to ensure no one suffers from a treatable condition simply because the right drug-disease connection hasn't been made.
Statistics & Facts
- There are 4,000 FDA-approved drugs for about 4,000 diseases, but 14,000 diseases still have no treatments available. (17:24) Dr. Fajgenbaum emphasizes that 80% of existing drugs are already generic, meaning there's no financial incentive to find new uses for them.
- A study in India of 1,600 breast cancer patients showed that lidocaine injection before surgery resulted in a 29% reduction in mortality at five years. (09:35) Despite being published in the Journal of Clinical Oncology and lidocaine costing only pennies per injection, this treatment has seen minimal adoption worldwide.
- The average small molecule drug can bind to between 20-30 different proteins in the body, yet most are approved for only one or two specific uses. (08:37) This represents a massive untapped potential for treating multiple conditions with existing medications.
