In this issue’s letter, I want to discuss the value of studying, and aiming to cure, rare diseases. This is prompted by a recent New England Journal of Medicine paper co-authored by Jeffrey Krischer, PhD, USF professor of pediatrics, and director of the Health Informatics Institute, on the treatment of lymphangioleiomyomatosis (LAM). LAM is a fatal lung disease that occurs in women with an incidence of 1 in 5 million.
Early in my career, when I was chief of pulmonary and critical care medicine at the University of Cincinnati, I met in my office a woman who told me that there were two teenagers in the same high school in Cincinnati with LAM. She wanted to know why so little was known about the disease and what could we do about it. She partnered with a member of the faculty to begin the LAM Foundation. This ultimately led to foundation and NIH-based funding to study the root cause of the disease. I am sure that there were naysayers who felt such funding was inappropriate due to the small number of affected patients. Or, in today’s vernacular, there would be an insufficient “return on investment to help the general public.”
In LAM, smooth muscle cells that circulate in the bloodstream land in the lung where they establish proliferative and destructive signaling networks. Basic science studies of LAM cells revealed inactivating mutations of the TSC locus, which leads to unchecked activity of mTOR. It didn’t take long to make the connection that a defunct antifungal drug, rapamycin, inhibits mTOR and could be a treatment for LAM. The aforementioned paper reported the definitive clinical trial of rapamycin, which included 89 patients. The deterioration of lung function in rapamycin-treated patients was markedly less than those treated with placebo. Not only are the results the ultimate proof-of-concept, they point towards a therapy for a terrible disease.
Along the way, the research on LAM taught us a tremendous amount about smooth muscle, growth factors, endothelial cells, and lung function – knowledge that can directly apply to common diseases such as asthma, emphysema, and pulmonary fibrosis. There are plenty of examples of basic, translational, and clinical sciences converging on a rare disease and leading to widely applicable insights into human biology.
So the next time someone suggests your research might not serve the greater good, remember LAM.
Sincerely,
Stephen Liggett, MD
Vice Dean for Research
Professor of Medicine, Molecular Pharmacology and Physiology
USF Health Morsani College of Medicine
