Gene therapy trial for Duchenne Muscular Dystrophy planned after successful tests in canines

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A team of researchers based at the University of Missouri has successfully treated dogs with Duchenne muscular dystrophy (DMD), by introducing a miniaturised version of the faulty dystrophin gene. They plan on starting a clinical trial to evaluate the treatment in humans shortly.

The various types of muscular dystrophy currently affect around 250,000 people within the United States, and occur when the body with replaces muscle tissues with fibrous, fatty or bony tissues in response to damage, causing loss of function. DMD, the common form of the disease affecting mainly boys, is caused by a genetic mutation that disrupts the production of an essential protein called dystrophin.

Professor Dongsheng Duan, leader of the study, which was published in Human Molecular Genetics this week, said; “This is the most common muscle disease in boys, and there is currently no effective therapy. 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.”

Loss of dystrophin causes a cascade of issues that eventually results in the death and degeneration of muscle tissues throughout the body. As the patients progress through life, everyday activities that rely on muscle activity, such as walking and breathing become extremely difficult and ultimately impossible, limiting both the quality and length of life.

Until now, the feasibility of using gene therapy techniques to replace dystrophin in patients has been severely limited, as it is one of the largest humans genes, with a primary mRNA transcript of around 2.4 megabases. “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 explained. “Through previous research, we were able to develop a miniature version of this gene called a microgene. This minimised dystrophin protected all muscles in the body of diseased mice.”

It has taken Duan and his team 10 years to refine their technique, so that the microgene is evenly distributed into all the muscles of an infected dog by the adeno-associated virus vector. As the dogs were of a relatable size to an affected boy, it is hoped that this foundation will allow rapid progression to human trials.

“The virus we are using is one of the most common viruses; it is also a virus that produces no symptoms in the human body, making this a safe way to spread the dystrophin gene throughout the body,” Duan concluded. “These dogs develop DMD naturally in a similar manner as humans. 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.”

Sources: Gene Therapy Treats All Muscles in the Body in Muscular Dystrophy Dogs; Human Clinical Trials Are Next Step, Press Release
Yue Y, Pan X, Hakim CH et al. Safe and bodywide muscle transduction in young adult Duchenne muscular dystrophy dogs with adeno-associated virus. Human Molecular Genetics. DOI