How a doctor cured his own terminal disease by repurposing existing drugs

Executive overview

Thousands of FDA-approved drugs are effective against diseases other than the ones they were approved for — but no system exists to find and apply those connections. Dr. David Fajgenbaum nearly died five times from Castleman's disease before discovering that sirolimus (rapamycin), a transplant drug, could put his disease into remission. He now runs EveryCure, a non-profit using AI to systematically match every approved drug to every disease it could treat.

The answers to many "untreatable" diseases may already exist inside the drugs we have — we just haven't looked.

The drug repurposing blind spot

• 4,000 FDA-approved drugs exist; 80% are already generic with no commercial incentive to find new uses
• The average small-molecule drug binds 20–30 different proteins, but is studied and approved for just one or two
• Patent economics drive companies to tweak formulations of existing drugs rather than find new disease indications
• Once a drug goes generic, all research and commercial development effectively stops
• Examples: aspirin reduces colon cancer recurrence; lidocaine injected before breast cancer surgery shows ~29% reduction in five-year mortality; colchicine (gout drug) now approved to reduce heart attack recurrence; thalidomide — once pulled for birth defects — later approved for leprosy and multiple myeloma

How information failure kills patients

• Castleman's disease patients in the US were dying while a Japanese drug (tocilizumab) was already proven and available — doctors simply didn't know
• DATA2 (a childhood stroke disease) went untreated for a decade despite a known cure (TNF inhibitors) because the knowledge wasn't disseminated
• The "Santa Claus theory": people assume a coordinated system is finding and delivering cures — in reality it is fragmented and random
• Outcome depends heavily on who you happen to know; people connected to academic medical networks get better outcomes
• Physicians lack time to read the literature systematically; their knowledge is largely frozen at residency plus conference summaries

Dr. Fajgenbaum's illness and self-directed research

• Diagnosed with idiopathic multicentric Castleman's disease as a third-year medical student at Penn; nearly died five times in three years
• Gained 100 pounds of fluid, needed daily transfusions, underwent dialysis, received last rites at age 25
• After the fifth near-death episode, began collecting his own blood samples and running lab experiments to characterise his immune dysregulation
• Found hyperactivation of the mTOR signalling pathway using serum proteomics and immunohistochemistry on his own lymph node
• Proposed sirolimus (rapamycin) to his physicians — a transplant rejection drug, never used in Castleman's — and went into remission; now 11+ years without relapse
• Key mindset: if seven off-label chemotherapies saved his life temporarily, an eighth or ninth drug might save it permanently

EveryCure: a systematic approach

• Uses AI and biomedical knowledge graphs to score every drug against every disease for potential new uses
• Nine active programs including lidocaine for breast cancer (lab and observational work) and DFMO (African sleeping sickness drug) for Bachman-Bupp syndrome in children
• Treats matching as a starting point; rigorous lab studies and clinical trials are still required before advocating clinical use
• Case studies: patient Al in Vancouver put into remission from Castleman's with adalimumab (TNF inhibitor), published in New England Journal of Medicine; Joseph (POEMS syndrome) pulled from life support using multiple myeloma drugs
• Distinct from one-off Hail Marys: goal is proving drugs work before patients reach crisis, so treatments are routine rather than experimental

How to navigate healthcare as a patient

• Connect with the disease organisation or advocacy group for your condition — they track what is being tried worldwide
• Identify the world's leading expert and seek a direct consultation; ask whether anything else is used anywhere else
• Keep asking questions: a second opinion is genuinely a different opinion, not a confirmation
• AI tools like Open Evidence are emerging for healthcare-oriented queries
• EveryCure accepts public submissions of off-label observations at everycure.org/ideas

The neuroscience of persistence

• Hope → action → impact → more hope forms a self-reinforcing circuit that mirrors function of the anterior mid-singulate cortex
• Electrical stimulation of this structure produces a sense of challenge bearing down combined with a drive to lean into it
• People who successfully overcome major obstacles and "super-agers" show maintained volume in this region relative to age-matched peers
• The circuit is also activated and strengthened by incremental goal-setting and athletic training — consistent with Fajgenbaum's experience as a Division I quarterback