Center for LAM Research and Clinical Care at BWH to conduct phase I combination drug trial

The Center for LAM Research and Clinical Care at Brigham and Women's Hospital (BWH) has been awarded a $1 million plus, four-year grant from the U.S. Department of Defense Office of the Congressionally Directed Medical Research Programs to fund their work on lymphangioleiomyomatosis (LAM). This work will be performed in partnership with the Massachusetts General Hospital and the National Heart, Lung and Blood Institute, Bethesda, Md.

LAM is a rare lung disease that affects women almost exclusively. In LAM, the normal lung tissue is progressively destroyed. LAM can also occur in women with a genetic syndrome called tuberous sclerosis complex (TSC), which causes tumors in different parts of the body, such as the skin, brain and kidneys.

LAM usually affects healthy, non-smoking, young women, according to Elizabeth Henske, MD, director of the Center for LAM Research and Clinical Care. Symptoms, such as shortness of breath, often begin in the late 20s, and can worsen with pregnancy. LAM can lead to lung collapse, oxygen dependency, the need for lung transplantation, and even death in young adulthood.

The center will use the funds to conduct a phase I clinical trial to determine the safety of a combination of two drugs to treat patients with LAM. The drugs that will be tested are hydroxychloroquine and sirolimus. Patients will be given different doses of the medications to find out which are deemed safe and efficacious. In addition to determining safety, the researchers will evaluate effects of the drug combo on patients' lung function, exercise capacity, kidney tumor size and quality of life.

Independently, hydroxychloroquine and sirolimus treat different conditions. Sirolimus is an immunosuppression drug that is given after organ transplantation, while hydroxychloroquine is used to treat rheumatoid arthritis and lupus.

"This will be the first time that this drug combination has been tested in women with LAM," said Henske. "We will learn whether the combination of [these] two drugs is safe in women with LAM. In our work in the laboratory, we have seen that this combination of drugs is more effective than either drug alone in models of LAM."