Rapamycin boosts cardiac and skeletal muscle function

SAN ANTONIO (July 25, 2012) — Rapamycin, a drug used in transplant patients to prevent organ rejection, may reverse cardiac and skeletal muscle defects as well, a new mouse study published today in Science Translational Medicine suggests. One of the authors is in the School of Medicine at The University of Texas Health Science Center San Antonio.

Rapamycin, a bacterial product, was isolated from Easter Island dirt in the South Pacific in the 1960s. In 2009 it received worldwide attention when three centers working independently — including a team at the Barshop Institute for Longevity and Aging Studies of the Health Science Center — showed that it slowed aging and increased life span in middle-aged mice.

In further work at the Health Science Center, rapamycin rescued learning and memory in mice with Alzheimer’s disease-like deficits.

In the new study, the drug reversed the elevated activity of a nutrient sensor called mTORC1 (mammalian target of rapamycin complex 1), improving cardiac and skeletal muscle function and enhancing survival of mice that lacked a gene called LMNA. Mutations in the LMNA gene may result in several conditions in affected individuals, including dilated cardiomyopathy (an enlarging of the chambers of the heart) and dystrophies of skeletal muscle and fat.

“The study made use of a novel formulation for oral delivery of rapamycin in food that was first developed and tested at the UT Health Science Center,” said paper co-author Randy Strong, Ph.D., professor of pharmacology in the School of Medicine and member of the Barshop Institute.

Dr. Strong, also a VA Senior Research Career Scientist, collaborated with Southwest Research Institute in San Antonio to develop a microencapsulated form of rapamycin that enabled long-term dietary studies of the compound to be conducted.

The research has several other ties to the Barshop Institute and the Health Science Center.

The first author, Fresnida Ramos, Ph.D., of the University of Washington at Seattle, did her doctoral training in aging with Feng Liu, Ph.D., a metabolic diseases researcher in the Department of Pharmacology and the Barshop Institute. Another author, Chen-Yu Liao, Ph.D., of the Buck Institute for Research on Aging in Novato, Calif., trained with Jim Nelson, Ph.D., in the Department of Physiology and the Barshop Institute.

“This is a nice paper demonstrating yet again the beneficial effects of chronic treatment with microencapsulated rapamycin, this time in a mouse model of accelerated aging, called progeria, and associated diseases,” said Z. Dave Sharp, Ph.D., professor of molecular medicine at the Health Science Center and member of the Institute for Biotechnology. “Importantly, the LMNA mouse models diseases presenting in progeroid patients, suggesting that rapamycin might be efficacious against them for an improved quality of life.”

The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving federal funding. Research and other sponsored program activity totaled $231 million in fiscal year 2011. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 28,000 graduates. The $736 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.

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