Researchers at the University of Florida's Health Mursani College of Medicine have identified a promising treatment pathway that may help protect the heart in people with Duchenne muscular dystrophy (DMD).
This disease is known to be hereditary and serious, leading to progressive muscle weakness and potentially causing life-threatening complications.
Duchenne muscular dystrophy primarily affects males, as it is inherited via the X chromosome. The disease leads to progressive weakness in the muscles responsible for movement and walking, but it becomes more serious when it affects the heart muscle.
The disease results from genetic mutations that prevent the body from producing the protein dystrophin, which is essential for maintaining the stability of muscle cells and protecting them from damage. Without this protein, muscles deteriorate over time, and healthy tissue gradually transforms into fat and fibrous tissue, impairing muscle function.
The heart is one of the organs most affected by the disease because it works continuously to pump blood throughout the body. As the heart muscle cells continue to be damaged, the heart may enlarge and its ability to pump blood may decrease, potentially leading to heart failure in advanced stages.
A new study, published in the journal Molecular Therapy, revealed that the experimental drug Setanaxib was able to preserve heart function, reduce myocardial hypertrophy, and limit the accumulation of scar tissue in laboratory models of the disease.
The study was led by Da-Chi Wang, director of the Center for Regenerative Medicine at the University of South Florida's Heart Health Institute, with the participation of a research team that included John Mably, Gabriella Deniz, and a number of collaborating researchers.
In the study, researchers tested the effect of the drug "Cetanaxib," which works to reduce what is known as oxidative stress, a process that occurs when levels of highly reactive molecules inside cells rise, which can lead to increased inflammation and the formation of fibrosis.
The drug targets the NOX1 and NOX4 enzymes, which are involved in the production of these molecules. Results showed that inhibiting this pathway helped improve cardiac function, reduce inflammation and fibrosis, and decrease the activity of genes associated with cardiomyopathy.
The results also indicated that the NOX4 enzyme may be a potential therapeutic target for the development of future drugs that help treat cardiomyopathy associated with this disease.
Mabley said the results represent an encouraging step, explaining that NOX4 enzyme inhibitors have previously been tested in clinical trials related to diseases such as pulmonary fibrosis, kidney and liver diseases, and that the next step may be to evaluate their use in Duchenne muscular dystrophy patients with the aim of slowing the development of heart complications.
This study comes after more than 15 years of research by Wang's team to understand the mechanisms of Duchenne muscular dystrophy development and to identify new biological targets that can be used to develop innovative treatments.
Denise emphasized that the study represents an important advance in heart disease and regenerative medicine research, and highlights the role of basic research in understanding human diseases and translating scientific discoveries into new therapeutic methods.
