Children with Duchenne muscular dystrophy (DMD) face a future of rapidly weakening muscles, which usually leads to death by respiratory or cardiac failure before their 30th birthday. While researchers are hopeful that gene therapy could eventually evolve into an effective treatment, few have targeted the heart of the problem as much as Dongsheng Duan, PhD.
Duan hopes a new $2.1 million grant he received from the National Institutes of Health will help him develop a treatment that prevents heart muscles from weakening as a result of DMD. As many as 40 percent of patients with the inherited disorder die from heart failure because their weakened cardiac muscles can't pump enough blood to sustain life.
Children with DMD, which is often seen in boys, experience weakening of both skeletal muscle and heart muscle due to a defective gene for dystrophin, a type of muscle protein. Researchers have developed a synthetic dystrophin gene that has shown to be effective in treating skeletal muscle, but Duan's findings published in the journal Molecular Therapy show that cardiac muscle requires different treatment. In fact, tests in an animal model have shown that treating skeletal muscle alone while leaving cardiac muscle untreated can lead to serious complications: Stronger skeletal muscles mean patients can be more physically active, which requires a stronger heart to pump blood throughout the body.
"We've demonstrated that the gene therapy that works for the skeletal muscle doesn't necessarily work for the heart," Duan said. "If we want a more comprehensive treatment, we cannot ignore how the disease affects cardiac muscle."
Duan's lab has analyzed data on thousands of patients with DMD to identify common patterns in deletions on the dystrophin gene that could have led to heart-specific muscle weakness. Now the researcher is developing a new synthetic gene that he hopes will comprehensively treat muscles weakened by DMD.
|Contact: Natalie Fieleke|
University of Missouri School of Medicine