Potential Drug Treatment for a Lethal Heart Disorder

August 21, 2012

A study by Columbia researchers showed that a form of dilated cardiomyopathy (DC) caused by mutations in the lamin A/C gene (LMNA) can potentially be treated with FDA-approved drugs. This form of DC is often associated with muscular dystrophy. Sixty percent of cardiomyopathy cases are DC, and the only cure is heart transplant. The form caused by the LMNA mutation progresses especially rapidly. A common kidney cancer drug successfully treated the condition in mice.

The mutation causes abnormal activation of a signaling pathway, which interferes with autophagy, a process by which a cell breaks down its components in response to low nourishment. Without sufficient autophagy, the heart cannot respond to increases in energy needs. The resulting muscle damage can lead to DC.

The researchers, including postdoctoral fellow Jason C. Choi, PhD, and led by Howard J. Worman, MD, professor of medicine and pathology and cell biology, gave the kidney cancer drug temsirolimus to mice with DC. The drug interrupted the abnormal signaling, which in turn reactivated the defective autophagy. Temsirolimus, which is one of a group of drugs called rapalogs, is already FDA-approved and on the market, shortening the time that would be required for clinical trials. If other forms of cardiomyopathy turn out to be caused by similar defects, these rapalogs may offer effective treatment.

“Temsirolimus Activates Autophagy and Ameliorates Cardiomyopathy Caused by Lamin A/C Gene Mutation” was published in Science Translational Medicine on July 25, 2012.

The research was supported by NIH grant R01AR048997, Muscular Dystrophy Association grant MDA172222, and a NIH Ruth L. Kirschstein National Research Service Award to Dr. Choi.