NASHVILLE, Tennessee—A microRNA called miR-128 seems to be involved in the pathology of Duchenne muscular dystrophy (DMD), according to a new study presented at the 2022 Muscular Dystrophy Association Clinical & Scientific Conference. Therefore, targeting it could be a novel therapeutic approach for patients with the disease.
Using different animal models of the disease, Anders Naar, PhD a professor of metabolic biology in the Department of Nutritional Sciences & Toxicology at the University of California, Berkeley, and his colleagues showed that miR-128 is highly present in muscles of animals with DMD. Circulating miR-128 is also elevated in the mouse and dog models of the disease as well as the plasma of patients with DMD.
Dr. Naar and his team then showed that targeting miR-128 using an antisense oligonucleotide dramatically decreased creatine kinase (CK) levels, a hallmark of muscle damage in DMD mice.
More importantly, inhibiting miR-128 reduced fibrosis and muscle fiber necrosis as well as grip strength in the animals. It also increased the size of skeletal muscle fibers.
“We have a mighty mouse with stronger and bigger muscles,” Dr. Naar said.
Read more about other experimental therapies for DMD.
Finally, miR-128 inhibition also de-repressed genes targeted by this miRNA, thereby decreasing inflammation in the mice.
The effect of the treatment lasted for more than 28 days following a single injection, Dr. Naar reported.
Experiments in a zebrafish model of DMD also showed that anti-miR-128 treatment decreased skeletal muscle abnormalities and increased the speed and distance traveled by the fish.
Because DMD also affects the heart, Dr. Naar and his team also assessed whether it is possible to target miR-128 in the heart and showed, using their mouse model, that indeed, a single injection of anti-miR-128 dramatically decreased levels of miR-128 in the heart.
Next, the team will be investigating whether this approach can improve dilated cardiomyopathy and heart failure.
“I hope I managed to convince you that microRNA . . . contributes to Duchenne muscular dystrophy,” Dr. Naar said, “We believe that this could represent a very attractive therapeutic target”.
Naar A. Therapeutic targeting of a pathological microRNA in DMD. Oral presentation at: 2022 Muscular Dystrophy Association Clinical & Scientific Conference; March 16, 2022; Nashville, TN.