“Fajgenbaum was having his last rites read to him, and his family braced for his death from Castleman disease, a rare inflammatory illness that impacts the lymph nodes and can severely damage other organs. But, in a rare stroke of skill and luck, Fajgenbaum was able to repurpose a generic drug, sirolimus, and go into remission.”
Article is interesting in the paths he used to find a treatment using AI.
“Oral sirolimus: For adults, loading dose of 5 mg/m^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. For children, 2 mg/m^2/day, target trough level 5-15 ng/mL by HPLC. This study is a Phase II open label study of daily administration of sirolimus in up to 24 evaluable male or female adults. Participants with iMCD who have failed previous therapy will take daily oral sirolimus for 12 months”
The latest Humans of New York features a man who was saved by repurposing sirolimus for his rare disease. Humans of New York
"I remember taking my final exam, getting stuck on an answer, and thinking: Who cares, I’m about to die. I knew something was very wrong. Medical school is always tiring, but this was a different kind of tired. I was getting by on multiple cups of coffee, multiple energy drinks. Large lumps had begun to appear in my neck. After the exam I stumbled down the hall to the ER and the doctors told me that my organs were failing. It took eleven weeks to make a diagnosis: a rare disease called Castleman’s. But there was no cure. A priest read me my last rites. I said goodbye to my family and prepared to die. But a last-minute dose of chemotherapy saved my life.
Over the next year I relapsed three times. Each one almost killed me. The last was the worst: I spent a month in the ICU, and it took seven different chemotherapies to bring me back. By then I’d reached the maximum dose of chemo a human can tolerate. The doctors told me I was out of options, and the next relapse would certainly kill me. I only had one hope. A tiny hope, but a hope. I had to cure the disease myself. It takes a billion dollars and ten years to create a new drug; I didn’t have the money or time. My only chance was to discover an existing drug that would work. I made spreadsheets of every similar disease and every drug used to treat it. I wrote over 2000 emails to every doctor who’d published a paper on Castleman’s. I started studying samples of my own blood, but I ran out of time.
Another relapse put me back in the ICU; from my hospital bed I asked the doctor to cut out one of my lymph nodes. I took it to the lab and discovered a particular protein called mTOR that was sending my immune system into overdrive. And that’s when I knew. I knew from my research that a drug called Sirolimus inhibits mTOR. My doctor was hesitant to prescribe it; there was no research to support my theory. But he took a chance, and within days my symptoms began to disappear. I still take the pill every day, eleven years later. I was able to marry my wife and have two beautiful kids. And through my work I’ve been able to save thousands of lives, by repurposing fourteen different drugs to treat rare diseases."
Epilogue:
In 2022, David Fajgenbaum co-founded Every Cure, a nonprofit organization on a mission to save and improve lives by repurposing existing medicines to treat devastating diseases.
Thank you. Every Cure seems to be doing some laudable, interesting work. I spent about 30 minutes looking at the site, and I appreciate their approach and methodology.
And yet, I was unable to put my hands on the actual tool, despite my concerted effort to do so. No doubt I’ve overlooked something obvious, but still… they claim open source, and imply it’s ready, and I can’t find it. If you can, let me know? ROADMAP tool | ROADMAP
Topol: I recently had a chance to read your amazing book, Chasing My Cure.It is quite a story. Let’s go back to 2010 when you picked up that something wasn’t right about your health, after having been the picture of health: bench-pressing 375 pounds — friends called you The Beast. But then something went off the track. Maybe we could start at that point.
Fajgenbaum: I was a healthy, third-year medical student, never had any health problems in my whole life. And then out of nowhere, I started feeling more tired than ever before. You remember during training — we were sort of always tired, right? In that context, what is feeling more tired than ever before? But it felt different. Then I noticed some lumps and bumps in my neck, which turned out to be enlarged lymph nodes. I noticed fluid pooling around my ankles, which seemed unusual, and this horrible abdominal pain. It got worse and worse over the course of a couple of weeks. I was on an ob/gyn rotation. I went from taking my medical school exam for ob/gyn to walking down the hall to the emergency department.