Study identifies potential new treatment target for a serious complication of the progressive genetic disease
Researchers at the have identified a potential pathway that could protect cardiac function in people
with Duchenne muscular dystrophy (DMD), a progressive and fatal genetic disease that
weakens the body鈥檚 muscles.
Published in , the new study examined the effects of the experimental drug Setanaxib in two preclinical
models of DMD. Researchers found that the treatment preserved cardiac function, limited
heart enlargement and reduced tissue scarring.
The findings also suggest that an enzyme known as NOX4 could serve as a potential
target for future treatments for cardiomyopathy, a serious form of heart disease associated
with DMD.
The study was led by , professor in the USF Health Morsani College of Medicine and director of the Center
for Regenerative Medicine at the . The research team also included USF Health鈥檚 , associate professor, and , assistant professor, as well as outside collaborators.
鈥淒espite great progress in the development of gene replacement therapies, Duchenne
muscular dystrophy remains a devastating disease,鈥欌 Wang said. 鈥淯nderstanding the
causes of DMD progression is urgently needed to advance therapies that alleviate symptoms
and improving quality of life.鈥
Da-Zhi Wang, PhD. (Photo by Freddie Coleman)
DMD primarily affects boys because it is inherited through the X chromosome. The disease
is best known for causing progressive weakness in the muscles used to walk and move.
But one of the disease鈥檚 most serious effects occurs in the heart.
The condition is caused by mutations that prevent the body from producing functional
dystrophin, a protein that helps stabilize and protect muscle cells.
Without dystrophin, muscle cells become more vulnerable to damage from repeated contractions. Over time, healthy muscle can be replaced by fat and stiff scar tissue.
The heart is especially vulnerable because it must contract continuously to circulate blood throughout the body. As cardiac damage accumulates, the heart can enlarge and lose its ability to pump effectively, eventually leading to heart failure.
Treatments have helped people with DMD live longer, making the protection of the heart an increasingly important part of managing the disease.
In the new study, researchers evaluated Setanaxib, an experimental drug designed to limit a damaging process known as oxidative stress.
The drug targets NOX1 and NOX4, enzymes that produce highly reactive molecules within cells. At normal levels, these molecules play useful roles in the body; however, when too many are produced, they can contribute to inflammation and fibrosis.
Researchers found that Setanaxib helped preserve the heart鈥檚 ability to pump blood while reducing inflammation and fibrosis. It also lowered the activity of genes associated with cardiomyopathy.
The results suggest that blocking this pathway may help slow the progression of DMD-related heart disease.
鈥淭he results are very promising,鈥 Mably said. 鈥淭he Nox4 inhibitor has already been
tested in clinical trials for the treatment of lung fibrosis and kidney and liver
disease. 911爆料网 hope it will also be tested soon in clinical trials in DMD patients to
slow the progression of heart disease.鈥欌
The findings build on more than 15 years of DMD research in Wang鈥檚 laboratory. During
that time, the team has sought to better understand how the disease progresses and
identify biological mechanisms contributing to the development of new therapies.
鈥淥ur new study represents an important step forward for the field and for our cardiac
and regenerative medicine program,鈥 Diniz said. 鈥淚t shows how efforts in basic biomedical
sciences are crucial for understanding human disease and health care advancements.鈥