Slowing Down Muscular Dystrophy

A team of researchers is reporting that by manipulating TAK1, a signaling protein that plays an important role in development of the immune system, they can slow down disease progression and improve muscle function in Duchenne muscular dystrophy (DMD).

DMD, caused by mutations in the dystrophin gene. DMD patients undergo severe muscle wasting, inability to walk and eventually death in their early thirties due to respiratory failure. 

“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,” said Ashok Kumar, Else and Philip Hargrove. “Our research shows that activating TAK1 can stimulate myofiber growth in a model of DMD, with no negative impact on muscle health.”

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

“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,” said Anirban Roy, research assistant professor.

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

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Sources:

Anirban Roy, Tatiana E. Koike, Aniket S. Joshi, Meiricris Tomaz da Silva, Kavya Mathukumalli, Mingfu Wu, Ashok Kumar. Targeted regulation of TAK1 counteracts dystrophinopathy in a DMD mouse model. JCI Insight, 2023; 8 (10) DOI: 10.1172/jci.insight.164768

University of Houston. “Discovery slows down muscular dystrophy: University of Houston researchers target protein that can slow disease progression, improve muscle function.” ScienceDaily. ScienceDaily, 24 May 2023. <www.sciencedaily.com/releases/2023/05/230524181848.htm>.

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