Lymphangioleiomyomatosis is a daunting name for an equally daunting disease. Called LAM, for short, it’s a rare but frequently fatal lung condition that affects almost exclusively women, usually in the prime of their lives, as they begin their careers and start families. Tumor-like masses grow in the lungs and together with the formation of lung cysts can lead to shortness of breath, cough, chest pains, collapsed lung and sometimes lung transplantation.
Clinicians and scientists at the University of Rochester Medical Center are working to improve the lives of LAM patients with the establishment of an official LAM Clinic – one of 26 sites in the nation designated by The LAM Foundation and the only clinic in Western New York. They’ve also developed a new animal model of the disease, which they’re using to study the origins of the disorder and to test new therapies.
Stephen R. Hammes, M.D., Ph.D., chief of the Division of Endocrinology and Metabolism, Patricia J. Sime, M.D., FRCP, chief of Pulmonary and Critical Care Medicine, and Mary Anne Morgan, M.D., Assistant Professor of Pulmonary and Critical Care Medicine, are spearheading URMC’s efforts.
In 2008, Hammes was invited to speak at a LAM Foundation meeting. He didn’t know much about the disease back then, but given his expertise in hormone signaling, meeting organizers thought he could shed some light on estrogen’s possible role in this predominantly-female condition.
“When I went to the meeting for the first time I met a lot of women with LAM and their families,” said Hammes. “This is by far the most motivated group of patients I’ve ever seen; you can’t help but be inspired by them and want to help them further their cause of understanding and finding treatments and a cure for the disease.”
Hammes received a $150,000 grant from The LAM Foundation to study a mouse model that closely mimics the disease in humans. While progress has been made in diagnosing and treating LAM, it remains a very mysterious disorder, partly because of the lack of useful animal models.
Scientists know that LAM legions strongly resemble benign or harmless tumors called leiomyomas, which are found in the wall of the uterus. LAM cells also contain mutations that deactivate or turn off certain tumor suppressor genes, allowing for the irregular growth and spread of cells. Based on these observations, scientists in Hammes’ lab and researchers at Baylor College of Medicine wondered if LAM-like lesions may actually originate in the uterus and spread to the lungs.
To test this theory, the team created a model that knocks out specific tumor suppressor genes in the uterus: Not only did these mice develop uterine tumors, but many of them developed tumors in the lungs as well.
“This is an exciting discovery because it demonstrates that LAM cells can indeed come from the uterus and enter the lungs,” said Hammes. “Not only does it support our hypothesis, but, more importantly, this mouse model may help us better understand how LAM cells grow and migrate, and may serve as a useful platform for testing new treatments for LAM.”
On the patient care side, Sime and Morgan will head URMC’s LAM clinic. The LAM Foundation, which provides education and support for patients and raises funds for research, mandates that LAM clinic sites have the capacity to accurately diagnose and treat the disease, as well as manage its many complications, including lung dysfunction, collapsed lung, and neurologic, dermatological and other manifestations.
Sime will lead a team that includes pulmonologists, endocrinologists, nephrologists, radiologists, pathologists, dermatologists and obstetricians and gynecologists with expertise in LAM diagnosis. Cardiothoracic surgeons specializing in the treatment of collapsed lungs and lung transplantation, respiratory therapists, nutritionists, and physical therapists will also contribute to patient care. The clinic may also be asked to serve as a clinical trial site for LAM-related research.
Buffalo-area LAM patient Katie McKenna is thrilled to have a LAM clinic closer to home. “This is truly a breath of fresh air,” she said. “Knowing that there is a place just an hour away where doctors specialize in this disease is very exciting.”
The nearest designated LAM clinics are at the Cleveland Clinic in Ohio and New York-Presbyterian Hospital in New York City.
Christina Selian of Rochester also has LAM. For the past few years she’s traveled to NIH for testing that’s part of a long-term study on the disease. While she’s very happy to contribute to the research, she says it is always tough to be away from home and without your family. “Having a LAM clinic here in Rochester is so convenient and comforting. I feel very fortunate to live in such an inspired and progressive medical community.”
Aside from Hammes, Sime and Morgan, Scott E. Liebman, M.D., M.P.H., associate professor of Nephrology, Carolyn E. Jones, M.D., associate professor of Surgery, Christian G. Peyre, M.D., assistant professor of Surgery, Haodong Xu, Ph.D., professor of Pathology and Laboratory Medicine, Mary Gail Mercurio, M.D., professor of Dermatology, Wendy Vitek, M.D., assistant professor of Obstetrics and Gynecology, and Susan K. Hobbs, M.D., Ph.D., assistant professor of Imaging Sciences, will make up URMC’s LAM team.
For more information about LAM, visit www.thelamfoundation.org or call 513-777-6889. To schedule an appointment at URMC’s LAM clinic, call 585-275-4161.