Gene Therapy - Scientist clears hurdles for muscular dystrophy therapy

Scientist clears hurdles for muscular dystrophy therapy
New studies demonstrate effective way to deliver gene therapy; MU scientist proves therapy can be beneficial for the heart

COLUMBIA, Mo. — Approximately 250,000 people in the United States have some form of muscular dystrophy. Duchenne muscular dystrophy (DMD) is the most common type of the disease, predominantly affecting males. Boys with DMD will lose the ability to walk by their teens and typically die before the age of 30. For years, scientists have studied the use of gene therapy as a possible way to correct the muscle deterioration, but hurdles such as the need to treat all muscles in the body, including both skeletal muscle and heart muscle, have challenged researchers looking for an effective therapy until now.

In recent studies, published in Molecular Therapy and Human Gene Therapy, a team of University of Missouri researchers, led by Dongsheng Duan, associate professor of molecular microbiology and immunology, has found not only a delivery method that can reach every muscle of the body in a large animal model, but a therapy that will work on both skeletal muscle, the type found in arms and legs, and cardiac muscle, such as the heart.

"The difficult challenge with treating Duchenne muscular dystrophy, and other types of muscle-related diseases, is that the therapy must reach almost every muscle throughout the body," Duan said. "We have found that our new therapy, which uses a particular virus to deliver the gene therapy, reaches all of the muscles in large animals. This development raises the hope of whole body correction of Duchenne muscular dystrophy."

Patients with Duchnne muscular dystrophy have a gene mutation that disrupts the production of a protein known as dystrophin. Absence of this protein starts a chain reaction that eventually leads to muscle cell degeneration and death. Eventually, the damaged muscle tissue is replaced by fibrous, bony or fatty tissue and loses function. In the heart, this leads to severe heart disease and can place severe limitations on individuals afflicted with the disease.

In gene therapy, mutated genes are replaced with healthy genes. However, even with gene therapy, the healthy genes must reach every muscle in the body. Previously, scientists, including Duan's team, have experimented using viruses to deliver the healthy genes. However, these earlier studies were conducted in mice. Duan's team has now proven that this delivery system will reach every muscle in larger animals, such as dogs.

"Between 40 percent and 60 percent of the body weight is muscle, so it's vital that we find a way to deliver the therapy to every muscle in the body," Duan said. "Since dogs are 250 times the size of mice, but only nine times smaller than a human on average, we have taken a significant step in understanding if this therapy can work."

Duan's team has not stopped with just that discovery. In gene therapy, it is not feasible to fix every cell in the heart. Previously, scientists were uncertain whether partial correction could benefit patients. In an earlier study, Duan's research team demonstrated that heart tissue could be corrected enough to sustain a healthy life if only 50 percent of the tissue was affected by the therapy. Following the success with heart tissue, Duan's team has demonstrated for the first time that this result also is true with live heart muscle.

The Mizzou researchers delivered the therapy to the hearts of newborn mice with muscular dystrophy and found that gene therapy corrected many of the electrocardiogram abnormalities in these mice.

New tests have been developed to screen newborns with a high risk of muscular dystrophy. With few treatments available, the screening has not been widely accepted, but that may change if Duan's therapy proves to be effective.

"If you can treat an infant before they develop symptoms, you can treat the patient before they experience muscle loss," Duan said. "If you wait until symptoms start to appear, the muscle has already started to deteriorate. It's very difficult to treat when there is no muscle there."


Duan's research has been supported by grants from the Muscular Dystrophy Association, the National Institute of Arthritis and Muscular Skeletal and Skin Diseases, and the National Institute of Neurological Disorders and Stroke.

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two years is a long time to wait. Is anyone aware if more will be recruited in the next two years. I thought product launch was going to take place in 2010- see ASKLEPIOS website
Just want to share- Dr.Mendell's team has their own database for interested patients. I asked them if they use duchenne connect and she said no. I have added my son to their database as well.
gotta link for their DB? thnx.
No link, guess it is not online. You need to send an email to and ask her to add to the db.
ok, thnx for the info. ;-)
MU team hopes dogs lead to treatment
Researchers target muscular dystrophy.

By JENNA YOUNGS of the Tribune’s staff
Published Saturday, January 10, 2009

Parker Eshelman photo
Dongsheng Duan, center, and his team of research assistants at the University of Missouri are using gene therapy to treat Duchenne muscular dystrophy in dogs, which they hope will lead to treatment in humans. The most common neuromuscular disease of childhood, DMD is considered incurable but treatable.

Dongsheng Duan hadn’t planned to focus his research on muscular dystrophy when he set out to start his own lab. While earning his doctorate at the University of Pennsylvania, he worked with a mentor on cystic fibrosis research.

"I was kind of forced to work on" muscular dystrophy, he said with a laugh. "He suggested I move on to my own field - otherwise we’d be competing with each other."

Since 2002, Duan has worked at the University of Missouri as an associate professor and researcher in the Department of Molecular Microbiology and Immunology, focusing on using gene therapy to treat Duchenne muscular dystrophy.

DMD is caused by a gene mutation that affects the body’s ability to produce dystrophin proteins and leads to muscle cell degeneration. The disease almost exclusively affects males, with initial signs occurring in childhood. Most with Duchenne muscular dystrophy die by age 30, and about 40 percent of the patients die from heart disease, said Brian Bostick, a graduate student in the School of Medicine working as a research assistant in Duan’s lab.

Duan’s research seeks to replace mutated genes with healthy genes in skeletal and cardiac muscles.

In his latest research, Duan and his team injected healthy genes into adeno-associated virus, which doesn’t cause disease in humans. The virus is a medium to deliver the gene to muscle cells in newborn dogs bred with dystrophy. His lab previously conducted a similar study using mice, but Duan said success with dogs is a major step toward eventually testing the therapy in humans with Duchenne muscular dystrophy.

Mice are 250 times smaller than dogs, and dogs are only nine times smaller than humans, so using dogs as a large-animal model helps researchers adjust the gene therapy, he said. Dystrophic dogs also more closely mimic human symptoms of the disease than mice do.

"The dog is almost the only" animal "model that can reproduce human symptoms," he said. "In a dog, you can see dystrophies. One problem is scaling up. It’s important to confirm the therapeutic effect in the dog model rather than in infected" children. "They already have a miserable life, and we don’t want to make it worse."

Bostick, who has worked with Duan for four years, said he became interested in working on the team because of Duan’s interest in treating heart disease related to muscular dystrophy. Duan’s enthusiasm for his work also helped, Bostick said.

Duan "is really interested and passionate about getting to human use," he said. "Our ultimate goal is to get to the human treatment stage. The key is moving on to a larger model, and the dog is the next important step. We’re getting closer."

Duan said his research team is working to address research complications, including that the dystrophin gene is the body’s largest gene and is bigger than the adeno-associated virus. He said some projects have focused on finding a medium larger than the adeno-associated virus or splitting the gene to fit into the virus. "We’ve made a lot of progress on that" research, he said.

Duan said his lab produces between three and five research manuscripts per year and already has three ready for 2009. Duan’s research is funded by the Muscular Dystrophy Association, the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Neurological Disorders and Stroke, according to an MU news release.

Duan said this gene therapy work also could be applied to other diseases, including cystic fibrosis, and he hopes the projects eventually will be ready for human application. "The sooner the better," he said. "I have so many volunteers who have e-mailed me from all around the world. China, Russia - you name it, I have it."

Bostick said Duan’s enthusiasm for his work makes success likely.

"He’s the most hardworking person I’ve ever met," Bostick said. "If anyone is going to make a big stride, he’s going to be the key one. He loves doing it so much and wants to do it for the right reasons. It makes me excited to be in this field because there are people like him in it."

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