How A Doctor Cured His Own Terminal Disease | Dr. David Fajgenbaum

Summary

Dr. David Fajgenbaum, a professor of translational medicine at the University of Pennsylvania, shares how he nearly died five times from a rare immune disorder called Castleman disease before discovering a treatment by systematically searching existing approved drugs. His experience revealed a massive blind spot in medicine: thousands of approved drugs have untapped therapeutic potential for diseases beyond their original indication, yet no systematic effort exists to identify and deploy these repurposed treatments. He now runs a nonprofit called Every Cure to solve this problem at scale.

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Key Takeaways

• 4,000 FDA-approved drugs exist for ~4,000 diseases, but there are still 14,000 diseases with no approved treatment — and 80% of those drugs are already generic with no financial incentive to explore new uses.
• The average small molecule drug binds 20–30 different proteins in the body, meaning most drugs are already doing far more than what they’re approved for.
• Aspirin has been shown to reduce colon cancer recurrence, particularly in patients with mutations in the mTOR pathway, yet this is rarely applied in clinical practice.
• Lidocaine injected around breast tumors 8–10 minutes before surgery showed a 29% reduction in five-year mortality in a 1,600-patient Indian trial — yet has seen almost no clinical uptake.
• Colchicine (traditionally used for gout) has demonstrated substantial reduction in cardiovascular disease risk in patients who have had a prior heart attack, especially those with diabetes.
• Drug repurposing is systematically neglected because once a drug goes generic, no company is financially incentivized to fund trials for new indications.
• TNF inhibitors were found to stop strokes in children with the rare disease DADA2 — but it took years for this knowledge to spread, during which hundreds of children died.
• Patients should actively connect with disease advocacy organizations, seek the world’s leading expert in their condition, and always ask whether alternative or off-label treatments exist elsewhere in the world.
• Sleep deprivation may trigger dangerous cytokine storms — mouse studies showed sleep-deprived mice died from immune overactivation, including elevated interleukin-6, a key cytokine in Castleman disease.
• Fajgenbaum’s nonprofit Every Cure uses AI and biomedical knowledge graphs to systematically match every drug to every disease and is currently running nine active repurposing programs.

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Detailed Notes

The Core Problem: Drug Repurposing Is Broken

• There are 4,000 FDA-approved drugs and approximately 18,000 known human diseases.
• Most drugs impact 40+ biological pathways, but are approved and studied for only one or two.
• Once drugs become generic, all pharmaceutical R&D stops — no company will fund large trials for new indications because profits are too low.
• The result: potentially life-saving treatments sit unused, and patients die from “untreatable” diseases that already have solutions hiding in a CVS pharmacy.
• Drug companies do repurpose drugs before patent expiration, but typically into the same disease with a slightly modified formulation, not into genuinely new conditions.

Notable Examples of Drug Repurposing

Aspirin

• Known use: pain relief, blood thinning, heart attack prevention.
• Lesser-known use: reduces risk of colon cancer recurrence, particularly in patients with mTOR pathway mutations.
• Despite published evidence, this use is not standard practice.

Viagra (sildenafil) / Cialis (tadalafil)

• Sildenafil was originally developed for heart disease, then repurposed for erectile dysfunction.
• Also repurposed for pediatric pulmonary hypertension — children who couldn’t get adequate blood flow to their lungs can now live normal lives on sildenafil.
• Tadalafil was initially developed for prostate health and circulation, then later found to treat erectile dysfunction.

Thalidomide

• Originally developed as an anti-nausea drug for pregnant women.
• Caused catastrophic birth defects (limb malformation) due to its anti-angiogenic properties — it blocks blood vessel growth.
• That same mechanism was later found effective against leprosy and multiple myeloma, where tumor cells depend on excess blood vessel formation.
• Now FDA-approved for both leprosy and multiple myeloma, saving thousands of lives.

Lidocaine

• Standard use: local anesthetic (dentistry, surgery incision sites).
• A large trial of 1,600 patients in India found that injecting lidocaine around a breast tumor 8–10 minutes before surgery resulted in a 29% reduction in five-year mortality.
• Published in the Journal of Clinical Oncology — yet almost no clinical uptake worldwide.
• Cost: pennies per injection.
• Every Cure is conducting additional lab work and evidence review before broadly advocating its adoption.

Colchicine

• Traditional use: gout (has been used for ~3,000 years).
• Mechanism: anti-inflammatory effects, among others.
• A modified dose formulation received FDA approval for secondary cardiovascular prevention — reducing risk of recurrent heart attacks.
• Particularly effective in patients with prior heart attack and diabetes.
• Challenge: required a modified dose to generate a new patent, which is what enabled the clinical trials to actually happen.

Pembrolizumab (PD-1 inhibitor)

• Originally developed for melanoma and lung cancer.
• Fajgenbaum’s lab searched PubMed and found a 2013 paper showing 4 of 5 angiosarcoma tumors had elevated PD-L1 expression.
• No one had translated this laboratory finding into a clinical treatment in the 3 years since publication.
• They treated the first known patient (Michael) with a PD-1 inhibitor for metastatic angiosarcoma — he entered nine-year remission and recently walked his daughter down the aisle.
• Pembrolizumab now works in approximately 18% of angiosarcoma patients — transforming a uniformly fatal cancer into one where ~20% of patients survive beyond one year.

TNF Inhibitors and DADA2

• DADA2: rare genetic condition causing dozens of strokes from birth through teenage years.
• A physician treating a DADA2 patient used a leftover TNF inhibitor (made for vasculitis) — the child’s strokes stopped completely.
• The discovery wasn’t systematically shared for ~10 years; hundreds of children died who could have been saved.
• Now, TNF inhibitors are the standard treatment for DADA2, stopping strokes in children worldwide.

Tocilizumab (IL-6 inhibitor)

• Developed by Dr. Kazu Yoshizaki in Japan specifically for Castleman disease.
• Approved in Japan for Castleman’s; later repurposed and approved in the U.S. for rheumatoid arthritis and other autoimmune diseases.
• Works in approximately one-third of Castleman disease patients.

DFMO for Bachmann-Bupp Syndrome

• Bachmann-Bupp syndrome: rare genetic disorder causing elevated ODC1 enzyme, leaving children tube-fed and bed-bound.
• DFMO, a drug originally made for African sleeping sickness, is a covalent binder to ODC1.
• When started early, children have feeding tubes removed and gain significant function.

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Fajgenbaum’s Personal Medical Journey

• Diagnosed with idiopathic multicentric Castleman disease (iMCD) during his third year of medical school at Penn.
• Symptoms: enlarged lymph nodes, severe fatigue, abdominal pain, fluid retention in ankles.
• At peak illness: gained ~100 pounds of fluid, experienced temporary blindness in his left eye (retinal hemorrhage), required daily transfusions of red blood cells and platelets, placed on dialysis.
• Had last rites read at age 25.
• Required seven chemotherapies (Adriamycin, Cytoxan, Etoposide, Velcade, Enzalutamide, Rituxan, and others) to achieve remission.
• Experienced five near-death episodes