Discovery slows down muscular dystrophy

UH researchers target protein that can slow disease progression, improve muscle function.

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One in 3,600 male births has DMD, an inherited neuromuscular condition brought on by mutations in the dystrophin gene. Patients with DMD experience severe muscular atrophy, cannot walk and finally pass away in their early 30s from respiratory failure. Muscle fiber destruction and an inflammatory reaction are symptoms of the condition. Fat and fibrotic tissue eventually replace the muscle fibers, which results in severe muscle weakening.

In a previous breakthrough, scientists uncovered a surprising fact: TAK1 is essential for maintaining skeletal muscle mass, and activating TAK1 beyond normal levels can enhance skeletal muscle growth.

Researchers from the University of Houston, College of Pharmacy have discovered a way to slow the progression of Duchenne muscular dystrophy (DMD) and enhance muscle function by modifying the signaling protein TAK1. TAK1 is crucial for immune system development.

Ashok Kumar, Else, and Philip Hargrove, Endowed Professor and chair Department of Pharmacological and Pharmaceutical Sciences, whose results were published in JCI Insight, said, “Our results suggest that TAK1 (transforming growth factor β-activated kinase1) is a regulator of skeletal muscle mass. By specifically targeting this protein, we can suppress the death of muscle fibers, known as myonecrosis, and slow down disease progression in DMD.”

“Our research shows that activating TAK1 can stimulate myofiber growth in a model of DMD, with no negative impact on muscle health.”

For this study, scientists designed experiments to reduce or augment the levels of TAK1 protein in skeletal muscle at different stages of disease progression.

Anirban Roy, research assistant professor, said“Our experiments demonstrate that depletion of TAK1 activity during peak necrotic phase followed by re-introduction of TAK1 at post-necrotic phase leads to substantial improvement in muscle pathology.”

“Accumulating evidence suggests that regulation of immune response, autophagy, and metabolism along with gene correction therapy can be promising approaches to slow disease progression in DMD patients.”

Journal Reference:

  1. Anirban Roy, Tatiana E. Koike, Aniket S. Joshi, Meiricris Tomaz da Silva, Kavya Mathukumalli, Mingfu Wu, and Ashok Kumar. Targeted regulation of TAK1 counteracts dystrophinopathy in a DMD mouse model. JCI Insight. DOI: 10.1172/jci.insight.164768