A Doctor Tested a New Treatment on Himself. Now, It May Help Others with This Rare Disease.

A doctor's quest to understand his own rare disease led him to test an experimental treatment on himself.



Dr. David Fajgenbaum, above, has a rare disease known as Castleman disease. He identified a treatment for himself that may work for others.
(Image: © Penn Medicine)

A doctor's quest to understand his own rare disease led him to test an experimental treatment on himself, and it may have worked. The physician, Dr. David Fajgenbaum, an assistant professor at the University of Pennsylvania's Perelman School of Medicine, has been in remission ever since he first used himself as a "test subject" five years ago.

Now, a new study suggests Fajgenbaum's treatment may help others with this rare inflammatory disorder known as Castleman disease.

The new research shows that patients with severe forms of the condition, who haven't responded to previous therapies, may benefit from a treatment that targets a specific signaling pathway inside cells called the PI3K/Akt/mTOR pathway.

The work, published today (Aug. 13) in the Journal of Clinical Investigation, is one of the few occasions when the lead author of the report (Fajgenbaum) is also a patient in the study.

The doctor's quest began in 2010, when Fajgenbaum, who was then an athletic 25-year-old in medical school, suddenly fell ill. He developed swollen lymph nodes, abdominal pain, fatigue and an eruption of small red spots on his body, according to the report. Fajgenbaum's condition soon worsened and became life-threatening.

Fajgenbaum was eventually diagnosed with Castleman disease, which is actually a group of inflammatory disorders that affect the lymph nodes. About 5,000 people in the U.S. are diagnosed with some form of Castleman disease each year. Patients with Castleman disease may have a mild form of the disease with a single affected lymph node, while others have abnormal lymph nodes throughout their body and develop life-threatening symptoms, including organ failure.

Fajgenbaum has this more severe form, known as idiopathic multicentric Castleman disease (iMCD), which is diagnosed in only about 1,500 to 1,800 Americans each year, according to the report. The severe form of the disease is similar to several autoimmune conditions, but like cancer, it also causes an overgrowth of cells, in this case in the lymph nodes. About 35% of people with iMCD die within five years of the diagnosis. Although there is one approved treatment for Castleman disease, a drug called siltuximab, not all patients respond to the therapy.

Fajgenbaum fell into this group. No existing therapies helped him and his symptoms kept coming back — during the 3.5 years after his diagnosis, he was hospitalized eight times, the report said. But by studying his own blood samples, Fajgenbaum identified a possible clue to his illness. Right before a flare-up, he saw a spike in the number of immune cells called activated T cells, as well as an increase in levels of a protein called VEGF-A. Both of these factors are regulated by the PI3K/Akt/mTOR pathway.

Fajgenbaum hypothesized that a drug that inhibited this pathway may help with his condition. He turned to a drug called sirolimus, which inhibits this pathway and is already used to prevent organ rejection in kidney transplant patients. Fajgenbaum hasn't had a flare-up of symptoms since he started taking the drug in 2014.

In the new study, Fajgenbaum and colleagues report that two other patients with iMCD also showed increased levels of activated T cells and VEGF-A before their symptoms flared up. After treatment with sirolimus, both patients also showed sustained remission. So far, both patients have gone 19 months without a relapse.

"Our findings are the first to link T cells, VEGF-A, and the PI3K/Akt/mTOR pathway to iMCD," Fajgenbaum said in a statement. "Most importantly, these patients improved when we inhibited mTOR. This is crucial because it gives us a therapeutic target for patients who don't respond to siltuximab."

Although the new findings are promising, the study involved only three patients, and larger trials will be needed to show that this drug is an effective treatment for iMCD. Soon, Fajgenbaum and colleagues plan to start a clinical trial to test sirolimus in up to 24 patients with iMCD.

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