The researchers used the approach to successfully reverse symptoms in mice with a form of muscular dystrophy that damages the heart. They also tested the virus-based delivery method in monkeys and found that genes were readily absorbed by heart muscle cells, and that the effect persisted for months.
The findings, published in the online edition of Circulation Research, pave the way for studies in humans that could begin as soon as early next year for patients with Pompe disease, a rare form of muscular dystrophy that is usually fatal in the first year of life.
“Nine years ago we knew we could get long-term gene expression in the heart but it was with direct injection into the heart muscle and it was inefficient,” said University of Florida pediatric cardiologist Dr Barry Byrne. “The difference here is that we can deliver a much lower dose of the vector into a vein like any other drug, and the corrective gene collects in the heart.”
Scientists say gene therapy looks increasingly feasible for the treatment of cardiovascular conditions linked to faulty genes or congenital metabolic diseases, including atherosclerosis, stroke, muscular dystrophy and an enlargement of the heart muscle known as dilated cardiomyopathy. But efforts to begin testing it in people have been slowed by the need to find ways to deliver corrective genes easily and efficiently.
“There are many forms of adult heart disease that are now well-understood as having a genetic basis; all of the arrhythmias, problems that are due to a family of diseases called long Q-T syndrome, the heart failure category where many folks have been attempting to modify contractility with gene transfer,” said Byrne, who also is affiliated with the UF Genetics Institute. “We’re using the very same strategies used with medical treatment but without ongoing use of medications.”
“I equate it to the space program,” added Dr R Jude Samulski, director of the Gene Therapy Center at the University of North Carolina-Chapel Hill. “We don’t know who Neil Armstrong is yet, who’s going to be the one to make this work, but we know we’re going to the moon.”