Gene Therapy May Help Muscular Dystrophy Patients

Research May Lead to Future Treatments for Duchenne Muscular Dystrophy

Medically Reviewed by Laura J. Martin, MD on July 25, 2011
From the WebMD Archives

July 25, 2011 -- Scientists say they have successfully tested a new treatment that may one day help children with a severe form of muscular dystrophy.

Duchenne muscular dystrophy is caused by the absence of a protein that helps keep muscle cells intact. It affects about one in every 3,500 newborns and causes progressive muscle weakness and early death.

Children with the disease, who are usually boys, typically lose the ability to walk by age 12 and often die before age 25, usually from heart and lung problems.

Treatments aim to slow the gradual decline and manage symptoms. There's no cure.

Fixing a Flawed Gene

The new therapy uses a clever bit of genetic sleight-of-hand to repair an inherited defect in the blueprints the body uses to make the muscle protein dystrophin.

The treatment uses artificially created nucleotides, the building blocks of DNA and RNA, to mask the defect, helping cells to skip over the flawed part of the protein's instructions.

The end result is a shortened but functional protein.

To understand what the treatment does, Andrian R. Krainer, PhD, a professor molecular genetics at Cold Spring Harbor Laboratory in New York, says it helps to think of the protein as a long spring.

"If it's missing one of the ends, it cannot be anchored at both ends. But if it's missing some coils in the middle, it can still work reasonably well," says Krainer, who is testing this approach to treat a different disease, but was not involved in the research.

The treatment isn't a cure, but it may help people live longer with less disability.

"You're essentially converting a very severe patient to a Becker patient," says study researcher Ryszard Kole, PhD. Becker muscular dystrophy is a milder form of the disease.

Kole developed the theory behind the treatment while a professor of pharmacology at the University of North Carolina at Chapel Hill. He is now a senior vice president at AVI BioPharma, the company that's developing the treatment.

First Human Tests

The study, which is published in The Lancet, tested increasing doses of the artificial nucleotides in 19 Duchenne patients, who ranged in age from 5 to 15.

The nucleotides were matched to the exact kind of genetic defect that was shared by all the patients, and they were given by weekly intravenous infusion.

Researchers tested samples of muscle tissue before and after the treatments to check dystrophin levels.

Seven patients, nearly all of them on the two highest doses of the drug given in the study, saw their dystrophin protein levels increase on the treatment.

Two of the best responders saw their levels climb from 0.9% to 17% and from 2% to 18%.

"There really is reason to be excited," says Richard Moxley III, MD, a pediatric neurologist at the University of Rochester. Moxley treats patients with muscular dystrophy and helped pioneer the use of corticosteroids in the disease. He was not involved in the current research.

He says there are other approaches to treatment in development. "Among the different things that are out there, for me, this is the most straightforward, the least plagued with toxic reactions, and the most immediately promising."

None of the patients appeared to see any clinically significant benefits from the study medication. But study researcher Franceso Muntoni, a pediatric neurologist and professor of medicine in the Institute of Child Health at University College London, says some patients noticed that they had better stamina.

"However, it is important to be aware of the placebo effect in short studies like this," he says.

And he says that because of how the protein works, patients wouldn't necessarily see immediate benefits.

"Dystrophin is a protein that does not make muscle stronger. It protects muscles from further breakdown, as would a shock absorber in our cars," Muntoni tells WebMD.

There were three serious adverse events reported in the study. Two, a case of vomiting after anesthesia and a broken ankle, were judged to be unrelated to the treatment. The third, a serious heart problem, was possibly related to treatment, but may also have developed as part of the underlying disease.

Muntoni says they are already working on putting together a larger study that would follow patients for a longer period of time.

He says it's the first time they've been able to try to correct the specific, underlying genetic defect in human patients. "This is remarkable and, until a few years ago, completely unforeseen."

Show Sources


Cirak, S. The Lancet, July 25, 2011.

Andrian R. Krainer, PhD, professor of molecular genetics, Cold Spring Harbor Laboratory, N.Y.

Ryszard Kole, PhD, professor of pharmacology, University of North Carolina, Chapel Hill; senior vice president, AVI BioPharma, Seattle.

Richard Moxley III, MD, pediatric neurologist, University of Rochester, N.Y. 

Franceso Muntoni, pediatric neurologist; professor of medicine, Institute of Child Health, University College London.

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