WEDNESDAY, March 16 (HealthDay News) — An already approved transplant-rejection drug is the first treatment to show a benefit for women with a rare lung disease that has had no cure or, until now, even a treatment.
The drug, sirolimus (Rapamycin), improved both lung function and quality of life in women with lymphangioleiomyomatosis, or LAM, according to a study published online March 16 in the New England Journal of Medicine.
“To have a therapy for this disease is rare and special,” said the study’s lead author, Dr. Francis X. McCormack, a professor and director of pulmonary, critical care and sleep medicine at the University of Cincinnati and scientific director of the LAM Foundation in Cincinnati, which helped fund the trial and also recruited participants.
LAM is characterized by progressive loss of lung function from the invasion of abnormal muscle tissue that obstructs airways. According to the American Lung Association, as many as 250,000 women worldwide might have the disease.
Fifteen years ago, researchers made a breakthrough when they discovered that people with LAM have a genetic mutation that affects the activation of the enzyme mTOR, which is responsible for controlling the growth and spread of cells. Sirolimus, a drug that is usually prescribed to prevent the rejection of a transplanted organ, also prevents mTOR activity. The drug is also being tested to fight cancer.
A pilot study conducted by the same group of researchers and published in 2008 found that sirolimus did indeed benefit a small number of people with LAM.
Their new study involved 89 women with LAM who were randomized to take sirolimus in pill form or a placebo for a year. They were then followed for an additional year.
Though a measure of breathing function declined 12 percent in the placebo group during the first 12 months of the study, those in the sirolimus group stayed stable and also reported improved quality of life, the study found.
But after stopping the drug, women in the treatment group as well as the placebo group saw their lung function decline.
“There was stabilized lung function for as long as patients took the drug, but if they stopped, the decline resumed and paralleled that of the control group,” McCormack said. “It looks like we can stabilize lung function as predicted, but it looks like we need continuous exposure to derive a continuous benefit.”
The study also found that sirolimus inhibited the protein VEGF-D, which seems to play a role in both LAM and cancer.
One expert said the finding is important, but the jury is out on sirolimus’ long-term benefit.
“It’s a breakthrough because it’s the first time we’ve found a drug that can prevent the inevitable decline of lung function associated with LAM, yet it’s yet not clear if it’s going to make a dramatic difference in the lives of these unfortunate women,” said Dr. Norman Edelman, chief medical officer of the American Lung Association.
Edelman went on to note that most of the women with this disease are young — in their childbearing years — and would need to take the drug for “years and years and years for it to have an impact.” And the drug is certainly not benign. “Sometimes side effects are serious,” he said.
Sirolimus costs about $8 a tablet, and people take two tablets a day, McCormack said.
Another expert was impressed by the speed at which research into LAM has progressed.
“Fifteen years ago, very little was known about the disease, and 15 years later there is a treatment,” said Jill Raleigh, executive director of the LAM Foundation. “It’s mind-boggling.”
But, Raleigh stressed, the treatment isn’t likely to benefit everyone, and McCormack wants to do more research to see which patient populations might benefit the most.
“We have a long way to go,” Raleigh said. “It’s not a cure, but it’s hope.”
More information
The U.S. National Heart, Lung and Blood Institute has more on LAM.