A National Heart, Lung, and Blood Institute History and Perspective on Lymphangioleiomyomatosis

Abstract

The rapidly evolving progress in lymphangioleiomyomatosis (LAM) research is an ongoing story of exemplary patient advocacy, collaboration between private organizations and government, outstanding scientists, and good timing. LAM is a rare, slowly progressive disease characterized by the proliferation of smooth muscle-like cells and cystic lesions that gradually destroy the lungs. LAM also produces lesions in the lymphatic tissues and is often accompanied by renal angiomyolipomas. It may occur sporadically or it may be associated with tuberous sclerosis complex (TSC). LAM affects mostly young and middle-aged women and rarely affects men. In the mid 1990s, when the National Heart, Lung, and Blood Institute (NHLBI) first began supporting research on LAM, it was a disease of unknown origin with no effective treatment other than lung transplantation. Patients had no support network and were often being managed with high doses of progesterone or oophorectomy to abrogate the effect of estrogen. Since that time, establishment of LAM patient advocacy and support groups, increased support for research in LAM by the NHLBI, launching and completion of a LAM patient registry, and development of a LAM tissue bank have combined to result in substantial research accomplishments and progress in both basic and clinical LAM research. The role played by NHLBI in LAM research illustrates some of the unique features of the NIH in the American biomedical research enterprise. NHLBI's intramural program supported the first studies on this rare orphan disease, and established essential infrastructure to facilitate research. Patient registries and tissue repositories were created and made available to the scientific community. Patient advocates ensured that these resources were used and shared. Funding opportunities enabled investigators to link tissues and clinical data, rapidly advancing the cellular and molecular biologic understanding of the disease. Support of these activities is now more broadly supported, and the scientific opportunities explored by an increasing number of investigators. NHLBI looks forward to development of more effective therapies, bringing industry and other partners into this exciting field of science and medicine (Fig. 1). FIG. 1. Essential partners in biomedical research. Patient Advocacy LAM patients and patient interest groups have been and continue to be the vital core of the LAM research enterprise. They have participated directly in the research effort, giving, their time, blood, and tissues. LAM patients and advocates have also formed strong support networks, raised funds, organized patient and scientific meetings, lobbied, educated, served as advisors, and provided financial support for investigators, especially those at early stages of their careers. This effort was sparked by the parent of a LAM patient, and a tireless advocate who worked vigorously in the mid 1990s to garner support for developing a LAM patient registry and tissue bank. A “Labor of Love” campaign was launched that engaged patients, women's organizations, churches, schools, educators, and doctors in efforts to boost recognition and support for a registry. The timing was good for this type of patient involvement, as the scientific community was ripe for such a partnership following a decade of AIDS advocacy. The research establishment had come to appreciate patients working closely with investigators, having an active voice in the management of their disease, and lobbying vigorously for research and treatment. The LAM Treatment Alliance was created in 2005 and is accelerating LAM research by many means, including fund raising, creating a seminar series for investigators, sponsoring scientific meetings, awarding grants, and raising public awareness. (LAM Treatment Alliance website http://lamtreatmentalliance.org/index.html). The Alliance has been instrumental in aiding in the continued collection of tissue and distribution of materials.