Rapamycin, an immunosuppressant drug used in a variety of disease indications and under study in aging research labs around the world, improved function and extended survival in mice suffering from a genetic mutation which leads to dilated cardiomyopathy (DCM) and rare muscular dystrophies in humans. There are currently no effective treatment for the diseases, which include Emery-Dreifuss Muscular Dystrophy and Limb-Girdle Muscular Dystrophy. The familial form of DCM often leads to sudden heart failure and death when those affected reach their 40's and 50's.
In research published in the July 25, 2012 online edition of Science Translational Medicine, scientists from the Buck Institute and other organizations focused on mutations in the gene LMNA, which produces A-type lamins. Mutations in this gene are associated with at least 13 diseases, with DCM among the most common. DCM accounts for 60 percent of all cardiomyopathy cases. LMNA mutations may account for up to one-third of patients that are diagnosed as having DCM and conduction disease. DCM causes a thinning of the left ventricle and loss of cardiac function.
The study showed that deletion of the LMNA gene led to ramped up activity in the molecular pathway mTOR (mammalian target of rapamycin) and that treatment with rapamycin turns down the abnormal signaling. Senior author Brian K. Kennedy, PhD, President and CEO of the Buck Institute for Research on Aging, says treatment with rapamycin extended mouse lifespan by 60 percent in a relatively rapid onset model of disease.
"What's particularly exciting is that this work offers a therapeutic possibility where there has been none," said Kennedy. "This study, along with others, suggests that clinical trials of rapamycin and its derivatives be initiated for human patients suffering from this form of DCM."