How Existing Drugs Can Cure 'Incurable' Diseases: The Power of Drug Repurposing and Patient Advocacy

Dr. David Fajgenbaum, a professor of translational medicine and human genetics, shares his personal journey of curing his own terminal Castleman's disease by repurposing existing drugs. He highlights a significant blind spot in the medical system: many effective treatments, and even cures, for diseases deemed untreatable already exist in the form of FDA-approved drugs used for other conditions. This realization stemmed from his own near-death experience, where conventional treatments failed, but he recognized the potential of drugs not initially designed for his specific illness.

The podcast delves into the systemic reasons why these life-saving applications often go undiscovered or unutilized. The pharmaceutical industry's patent-driven model heavily incentivizes the development of new drugs or new formulations of existing drugs for their original indications, rather than exploring novel uses for generic medicines. With 80% of the 4,000 FDA-approved drugs already generic, there's little financial incentive for companies to invest in research for new applications, leaving 14,000 diseases without any treatment. Drugs are often approved for one or two pathways, despite impacting 20-30 different proteins and mechanisms in the body, creating a vast untapped potential for repurposing.

Several compelling examples of successful drug repurposing are discussed, including aspirin's use beyond pain relief to prevent heart attacks and reduce colon cancer recurrence, Viagra's application for a rare pediatric lung disease, and the fascinating case of lidocaine reducing breast cancer mortality by nearly 30% when injected before surgery. The tragic story of DADA2, where a life-saving TNF inhibitor treatment was known by one doctor for a decade but not widely disseminated, underscores the critical need for better knowledge sharing and systemic change. Thalidomide, infamous for birth defects, is also highlighted for its anti-angiogenic effects that treat leprosy and multiple myeloma.

Dr. Fajgenbaum, through his nonprofit Every Cure, is actively working to address this challenge by using biomedical knowledge graphs, AI, and machine learning to systematically identify and validate new uses for existing medicines. The episode emphasizes the crucial role of patient agency and self-advocacy. Practical advice includes connecting with disease-specific advocacy groups, seeking out world experts, and persistently asking questions about potential alternative or repurposed treatments, thereby empowering individuals to navigate their health journey more effectively and potentially uncover life-saving options.

"David, we've tried everything. We tried these chemotherapies, we tried this one experimental drug. There's nothing more that we can do."

"I'm going to dedicate the rest of my life, however long that's going to be, it might be a couple of days, maybe it'll be a couple of months, but however long I've got to try to find out, is there a drug out there that could help me and other patients with my disease that's made for another condition?"

"No one should suffer if there's a drug at your CVS that could help you."

"Most approved drugs impact at least 40 different pathways and mechanisms across the human brain and body, but these drugs are generally approved for use in just one or two of those pathways."

"Many effective treatments, and in some cases cures, exist to diseases that we are told are hopeless to treat, and that even the best trained and well-meaning MDs are often unaware of those treatments."

"The system really isn't set up to find new uses for old medicines."

"The average small molecule, so a drug that's approved for a condition, can bind between 20 and 30 different proteins in the body. So, we call a drug... We say it does one thing, but actually it's doing a lot of other things in the body..."

"If they had lidocaine injected around the tumor before surgery, eight to ten minutes before surgery, there was a 29% reduction in mortality at five years, versus those who did not have lidocaine injected."

"There's still 14,000 diseases that don't have a single treatment right now. And of the 4,000 drugs we have, 80% of them are already generic, which means that there is no incentive to find a new use for those medicines."

"The world knew, someone in the world knew that you could save kids' lives with a TNF inhibitor, but the world didn't know, and we hadn't gotten the word out about it."