The dystrophin protein connects the cytoskeleton of muscle fibers with its N-terminal actin-binding domain and the extra-cellular matrix via a cysteine-rich C-terminal domain that binds dystroglycan, which in turn is bound to laminin 2. Between these two functional domain lies a large central domain that consists of 24 spectrin like repeats.
Human clinical trials are next step. Muscular dystrophy, which affects approximately 250,000 people in the US, occurs when damaged muscle tissue is replaced with fibrous, fatty or bony tissue and loses function. For years, scientists have searched for a way to successfully treat the most common form of the disease, Duchenne Muscular Dystrophy (DMD), which primarily affects boys. Now, a team of researchers has successfully treated dogs with DMD and say that human clinical trials are being planned in the next few years.
“This is the most common muscle disease in boys, and there is currently no effective therapy,” said Prof. Dongsheng Duan. “This discovery took our research team more than 10 years, but we believe we are on the cusp of having a treatment for the disease.”
Patients with Duchenne muscular dystrophy have a gene mutation that disrupts the production of protein “dystrophin” leading to muscle cell degeneration and death. Affected boys lose their ability to walk and breathe as they get older. This places significant limitations on individuals afflicted with the disease. Dystrophin also is one of the largest genes in the human body.
“Due to its size, it is impossible to deliver the entire gene with a gene therapy vector, which is the vehicle that carries the therapeutic gene to the correct site in the body,” Duan said. “Through previous research, we were able to develop a miniature version of this gene called a microgene. This minimized dystrophin protected all muscles in the body of diseased mice.” The dog has a body size similar to that of an affected boy.
In this latest study, the MU team demonstrated for the first time that a common virus can deliver the microgene to all muscles in the body of a diseased dog. The dogs were injected with the virus at 2-3 months old and just starting to show signs of DMD. The dogs are now 6-7 m.o. and developing normally. ” It’s important to treat DMD early before the disease does a lot of damage as this therapy has the greatest impact at the early stages in life.” http://munews.missouri.edu/news-releases/2015/1022-gene-therapy-treats-all-muscles-in-the-body-in-muscular-dystrophy-dogs-human-clinical-trials-are-next-step/
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