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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printing the article and have an appt with Dr. Wong tomorrow morning! How timely!!! I will write as soon as I get to a computer, but that could be Friday afternoon. This is very interesting...I have to wonder why we (ok, well, I) have not heard of these folks before...
I will let you know what Dr. Wong says as soon as I can.
Thanks Lori. I hope they can begin some clinical trials soon.

This is amazing. Its all good news but if they do not start trialling it soon on the boys, then the boys who eventually loose all their muscle will not benefit. All these trials take years and years before any boys benefit and our boys do not have time. Its frustrating. I want to get excited and believe but time scares me. Everything takes too long.
This sounds like the awesome miracle we're all waiting for ... and I agree that the wait is horribly too long. But I'm thinking of my son at the moment-- 18 months old, no muscle loss yet, smaller than a dog .... Who do I have to bribe and how much?
Hey, I'm not sure my editing of my earlier post worked so here's the scoop. I looked this up on and got the contact info: Christian Basi, email

I emailed him; I'll let you know what happens.
Duan's work is good stuff. I read about him over a year ago. I believe after he publshed some of his work last year, he was invited to talk at the ActionDuchenne conference 2007 in the UK.

If memory serve's me correctly, he has a better version of AAV's....but memory hasn't been doing a great job serving me lately. :-(

Lori, please refresh my mind with good notes from Dr. Wong....I'm feeling too worn out to dig thru my notes from the past.
This article is all over my google alerts this morning but there dosn't seen to be any mention of when human trials might be a go. I hope Dr. Wong can answer that for us.
I happend to meet Pat last month when I was at Cinci and asked her regarding Gene Therapy trials and infact she was mentioning the same problem that this article seem to say they have overcome. Hope PPMD can look into this.

Here's the full text of the paper he published. A virus was used to induce a mini dystrophin gene in newborn mice with very positive effects on cardiac function. The article does not say whether the immune systems for the mice had been suppressed.
cardiac is the second part of discovery. I thought the first part talks about being able to reach all of the skeletal muscles.
I am familiar with Dr. Duan's work, which is very interesting for sure. And to be honest, I find these google alerts very difficult as they suggest something is 'around the corner'. The vector Dr. Duan is using a pair of optimized tsAAV vectors, which increases the packaging capacity. Dr. Ruan generated a set of optimized alkaline phosphatase (AP) tsAAV vectors and delivered AAV serotype 9 pseudotyped AP tsAAV intravenously to the dog model with good results. I do not believe this optimized tsAAV vector has ever been in human studies. (Jerry Mendell's recent single muscle clinical trial used AAV with different serotypes). While this is very interesting and certainly promising, it will take time before we see systemic delivery in boys.
I am not aware of any such trials with this vector, and I searched the gene therapy clinical trial website (Gemcris: and there wasn’t anything.
Warm regards,
There is definitely a very long way until this becomes a therapy if ever. We see how slow Dr. Mendell's trial is progressing, they started the single muscle trial in 2006 and it is still not completed.

With that in mind, the following statement doesn't sound promising for THIS generation of boys:
"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."

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