A physician's quest to understand his own rare disease led to him testing an experimental treatment for himself, and it may have worked. The doctor, Dr. David Fajgenbaum, assistant professor at the University of Pennsylvania's Perelman School of Medicine, has been in remission since he first used himself as a "test subject" five years ago.
A new study now suggests that Fajgenbaum's treatment may help others with this rare inflammatory disorder known as Castleman's disease.
The new research shows that patients with severe conditions who have not responded to previous treatments can benefit from a treatment that targets a specific signaling pathway within cells called the PI3K / Akt / mTOR pathway.
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The work, published today (August 1
The doctor's assignment began in 2010, when Fajgenbaum, who was then an athletic 25-year-old in medical school suddenly became ill. He developed swollen lymph nodes abdominal pain, fatigue and an outbreak of small red spots on the body, according to the report. Fajgenbaum's condition soon strengthened and became life-threatening.
Fajgenbaum was eventually diagnosed with Castleman's disease, which is actually a group of inflammatory disorders affecting the lymph nodes. About 5,000 people in the United States are diagnosed with some form of Castleman's disease each year. Patients with Castleman's disease may have a mild form of the disease with a single affected lymph node, while others have abnormal lymph nodes throughout the body and develop life-threatening symptoms, including organ failure .
Fajgenbaum has this more serious form, known as idiopathic multicentric Castleman's disease (iMCD), which is diagnosed in only 1,500 to 1,800 Americans each year, according to the report. The serious 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 diagnosis. Although there is an approved treatment for Castleman's disease, a drug called siltuximab, not all patients respond to the treatment.
Fajgenbaum fell into this group. No existing therapies helped him and his symptoms continued to recur – during the 3.5 years after his diagnosis, he was hospitalized eight times, according to the report. But by studying his own blood tests, Fajgenbaum identified a possible clue to his illness. Just before an inflation, he saw a spike in the number of immune cells called activated T cells, as well as an increase in the levels of a protein called VEGF-A. Both of these factors are regulated by the PI3K / Akt / mTOR pathway.
Fajgenbaum assumed that a drug that inhibits 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 patients with kidney transplantation . Fajgenbaum has not 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 prolonged remission. So far, both patients have gone 19 months without relapse.
"Our results are the first to link T cells, VEGF-A and the PI3K / Akt / mTOR pathway to the iMCD," said Fajgenbaum in a statement . "Most importantly, these patients improved when we inhibited mTOR. This is crucial as it provides us with a therapeutic target for patients who do not respond to siltuximab."
Although the new results are promising, the study involved only three patients, and larger studies will be needed to demonstrate 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.
Originally published on Live Science .