Duchenne muscular dystrophy, or DMD, is characterized by rapidly weakening muscles, usually leading to death by respiratory or cardiac failure. As many as 40 percent of patients with DMD die from heart failure — usually by age 30 — because their weakened cardiac muscles can’t pump enough blood.
Researchers are hopeful that gene therapy could eventually evolve into an effective treatment. But few have targeted the heart of the problem as much as Dongsheng Duan, professor of molecular microbiology and immunology at the MU School of Medicine.
Duan hopes a new $2.1 million grant from the National Institutes of Health will help him develop a treatment that prevents heart muscles of children with DMD from weakening.
Most often seen in boys, DMD is caused by a defective gene for dystrophin, a type of protein that keeps muscle cells intact. Researchers have developed a synthetic dystrophin gene that is effective in treating skeletal muscle, but Duan’s research, published in the journal Molecular Therapy, show that cardiac muscle requires different treatment. In fact, animal studies 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,” said Duan, a Margaret Proctor Mulligan Distinguished Professor in Medical Research. “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.
“We’re developing this gene based on what we already know about skeletal muscle, so it will not only be perfectly functional for skeletal muscle but also therapeutic for heart muscle,” said Duan, who plans to evaluate the newly developed gene in dystrophic mouse and dog models.
With additional funding from the NIH, Duan’s team is developing viral vectors for carrying the most important parts of the therapeutic genes to diseased muscle cells.
The therapy-carrying viruses will be injected directly into the blood system or the muscles. Following therapy, researchers will perform a series of tests to evaluate the strength of the heart muscle and the effect of the treatment.
“Cardiac and skeletal muscle need to be simultaneously treated in patients,” Duan said. “This is just the beginning of research on the heart muscle.”