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August 1, 2011

COLUMBUS, Ohio – Two common drugs used to treat heart failure might also improve heart and muscle function in Duchenne muscular dystrophy (DMD), according to a new study.

A team of researchers at The Ohio State University Medical Center discovered that early treatment with lisinopril and spironolactone significantly preserves heart and skeletal muscle tissue in an animal model of the disease.

“Despite the inevitable heart and skeletal muscle deterioration generally seen in Duchenne muscular dystrophy patients, this drug combination provides nearly normal muscle function and considerable preservation of tissue,” says Dr. Subha Raman, a cardiologist and associate professor of cardiovascular medicine at Ohio State’s Medical Center. “We are very encouraged by these results, yet we know clinical trials are needed,” says Raman, who worked with Ohio State scientists Jill Rafael-Fortney and Paul Janssen on the study.

The research is published in the American Heart Association’s journal Circulation.

DMD is an inherited disorder in which muscles rapidly weaken, and a majority of patients develop heart and respiratory failure and do not survive into their 30s. 

Currently, treatment begins after heart damage is detected in DMD patients.  The research team hypothesized that using the heart drugs earlier could prevent damage before it started. They tested three groups of mice with heart and muscle disease similar to that associated with DMD: one group was treated with the drugs beginning at four weeks of life, a second group began treatment at eight weeks of life and the third group was left untreated.  After 20 weeks, researchers observed the set with the earliest drug treatment had almost complete prevention of heart muscle damage and heart function was preserved at 80 percent of normal, while the heart function in the untreated set dropped to 32 percent of normal.

Similar results were seen with the preservation of skeletal muscle.  The group on the earliest treatment maintained 80 percent of normal function, compared to the untreated group whose skeletal function declined to just 40 percent of normal.

“While both lisinopril and spironolactone are shown to be extremely effective in patients with cardiovascular disease, we were surprised by their ability to prevent skeletal muscle damage as well,” says Raman.

“If these results directly translate in our future clinical trials, it could mean that DMD patients may never have to use wheelchairs and could live long and happy lives,” says Jill Rafael-Fortney, co-author and a scientist at Ohio State’s Medical Center. “I’ve spent 20 years in DMD research and I hope these drugs will actually make life-changing improvements for patients.”

The inspiration behind this research, 23-year-old Ryan Ballou of Pittsburgh, is a DMD patient who, along with his father, started BallouSkies to raise awareness and support Raman’s research of heart failure in muscular dystrophy patients.

“With their inspiration and support, we’ve accomplished in less than a year what would typically require three to five years if pursuing traditional means of support,” says Raman.

In addition to the promise this treatment could hold for DMD patients, the investigators expect that this finding could also have implications in other disorders involving heart and skeletal muscle damage.

Additional funding was provided by the Beckman Foundation, the National Institutes of Health and the American Heart Association.


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