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.
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.
LAM is a progressive, cystic lung disease that occurs almost exclusively in women. In LAM, an unusual type of smooth muscle cell grows uncontrollably and spreads from an unknown source to restricted areas in the body, including the lungs, lymph nodes and vessels and kidneys, limiting the flow of air, blood and lymph. Shortness of breath and recurrent lung collapse are common in patients with LAM, and until now, lung transplantation has been the only hope for patients who progress to respiratory failure. LAM affects about five people per million and occurs in 30 to 40 percent of women with tuberous sclerosis complex, a genetic disorder which also causes tumors to form in the kidneys, brain, heart and other organs. 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 American researchers and published in 2008 found that sirolimus did indeed benefit a small number of people with LAM.
In their new study they studied 89 women with LAM in the United States, Canada and Japan were randomised to take sirolimus in pill form or a placebo for a year. They were then followed for an additional year. Patients underwent baseline lung function testing, and lung function and exercise outcomes were measured over the course of six visits in the first year. Participants were also given questionnaires to determine how their symptoms changed throughout the course of the study.
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. But after stopping the drug, women in the treatment group as well as the placebo group saw their lung function decline.
There was stabilised lung function for as long as patients took the drug, but if they stopped, the decline resumed and paralleled that of the control group. The study also found that sirolimus inhibited the protein VEGF-D, which seems to play a role in both LAM and cancer.
Sirolimus' long-term benefit is a breakthrough because it's the first time researchers have 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.
Most of the women with this disease are young - in their childbearing years - and would need to take the drug for years for it to have an impact. And the drug is certainly not benign with sometimes serious side effects.
The researchers stressed that the treatment isn't likely to benefit everyone and further research is needed to see which patient populations might benefit the most and to determine the optimal dose and duration of treatment.
LAM is a progressive, cystic lung disease that occurs almost exclusively in women. In LAM, an unusual type of smooth muscle cell grows uncontrollably and spreads from an unknown source to restricted areas in the body, including the lungs, lymph nodes and vessels and kidneys, limiting the flow of air, blood and lymph. Shortness of breath and recurrent lung collapse are common in patients with LAM, and until now, lung transplantation has been the only hope for patients who progress to respiratory failure. LAM affects about five people per million and occurs in 30 to 40 percent of women with tuberous sclerosis complex, a genetic disorder which also causes tumors to form in the kidneys, brain, heart and other organs. 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 American researchers and published in 2008 found that sirolimus did indeed benefit a small number of people with LAM.
In their new study they studied 89 women with LAM in the United States, Canada and Japan were randomised to take sirolimus in pill form or a placebo for a year. They were then followed for an additional year. Patients underwent baseline lung function testing, and lung function and exercise outcomes were measured over the course of six visits in the first year. Participants were also given questionnaires to determine how their symptoms changed throughout the course of the study.
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. But after stopping the drug, women in the treatment group as well as the placebo group saw their lung function decline.
There was stabilised lung function for as long as patients took the drug, but if they stopped, the decline resumed and paralleled that of the control group. The study also found that sirolimus inhibited the protein VEGF-D, which seems to play a role in both LAM and cancer.
Sirolimus' long-term benefit is a breakthrough because it's the first time researchers have 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.
Most of the women with this disease are young - in their childbearing years - and would need to take the drug for years for it to have an impact. And the drug is certainly not benign with sometimes serious side effects.
The researchers stressed that the treatment isn't likely to benefit everyone and further research is needed to see which patient populations might benefit the most and to determine the optimal dose and duration of treatment.
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