Discovery slows down muscular dystrophy
University of Houston researchers target protein that can slow disease progression, improve muscle function

Date:
May 24, 2023
Source:
University of Houston
Summary:
A research team has discovered that by manipulating a certain
protein in the immune system they can slow down disease progression
and improve muscle function in Duchenne muscular dystrophy.


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FULL STORY ==========================================================================
A team of researchers at the University of Houston College of Pharmacy 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 dystrophin gene, is an inheritable
neuromuscular disorder that occurs in one out of 3,600 male births. DMD patients undergo severe muscle wasting, inability to walk and eventually
death in their early thirties due to respiratory failure. The disease is
marked by an inflammatory response and death of muscle fibers. Eventually,
the muscle fibers are replaced with fat and fibrotic tissue that causes
severe muscle weakness.

"Our results suggest that TAK1 (transforming growth factor b-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 Endowed Professor and chair,
Department of Pharmacological and Pharmaceutical Sciences, whose results
were published in JCI Insight. "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.

For this research, supported by the National Institutes of Health,
the team designed experiments to reduce or augment the levels of TAK1
protein in skeletal muscle at different stages of disease progression.

"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.

The current standard of care for DMD is focused on reducing inflammation
with corticosteroids, which modestly reduces disease progression, but
has serious side effects.

"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.

* RELATED_TOPICS
o Health_&_Medicine
# Muscular_Dystrophy # Fibromyalgia # Fitness #
Chronic_Illness # Joint_Pain # Neuropathy # Healthy_Aging
# Human_Biology
* RELATED_TERMS
o Immune_system o AIDS o Protein o Physical_exercise o Meat
o Blood_vessel o Botulinum_toxin_(cosmetic_treatment) o Artery

========================================================================== Story Source: Materials provided by University_of_Houston. Original
written by Laurie Fickman. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. 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 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/05/230524181848.htm

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