Heart-function protein may help muscular dystrophy patients live longer

January 14, 2020

A Rutgers-led team may have found the key to preventing Duchenne muscular dystrophy (DMD)-related heart disease, the leading cause of death in patients living with the disease.

The study, published in the Journal of Clinical Investigation (JCI), examined the role of Connexin-43 (Cx43), a protein that regulates heart function. The researchers found that Cx43 was dysfunctional in both human and mouse DMD hearts, so they modified the Cx43 protein in the hopes of alleviating heart disease. The researchers discovered that altering the Cx43 protein through a process called phosphorylation protected DMD mice against irregular heart beat and late-stage failure.

"For many DMD patients, the heart muscles gradually break down, leading to death. Our findings may help give hope to millions of patients," said study co-author Diego Fraidenraich, an assistant professor of Cell Biology and Molecular Medicine at Rutgers New Jersey Medical School.

"Medical advances have managed to slow down the disease progression in most muscles in the body, but there are yet to be any discoveries that target or prevent deterioration of the DMD heart, which remains the number one killer among these patients," said co-author Eric Himelman, a PhD candidate at Rutgers New Jersey Medical School. "Therapies based on our finding may help prolong the lives of muscular dystrophy and other heart disease patients."

DMD, a genetic disorder characterized by progressive muscle degeneration, is the most common type of muscular dystrophy, affecting about one in 5,000 males and typically beginning at about age 4. The average life expectancy is 26.

These findings were simultaneously published together in JCI insight with another Rutgers-led study that examined Cx43 activity in the heart

Next steps include developing drugs that directly target Cx43 in DMD hearts, with a goal of potentially introducing clinical trials using Cx43 modification as a therapy for DMD patients.

The study was funded by the National Institutes of Health, the Muscular Dystrophy Association and the American Heart Association, and includes an interdisciplinary team of investigators with complementary expertise from Rutgers University, Fred Hutchinson Cancer Research Center, New York University and Baylor College of Medicine.

Rutgers University

Related Muscular Dystrophy Articles from Brightsurf:

Using CRISPR to find muscular dystrophy treatments
A study from Boston Children's Hospital used CRISPR-Cas9 to better understand facioscapulohumeral muscular dystrophy (FSHD) and explore potential treatments by systematically deleting every gene in the genome.

Duchenne muscular dystrophy diagnosis improved by simple accelerometers
Testing for Duchenne muscular dystrophy can require specialized equipment, invasive procedures and high expense, but measuring changes in muscle function and identifying compensatory walking gait could lead to earlier detection.

New therapy targets cause of adult-onset muscular dystrophy
The compound designed at Scripps Research, called Cugamycin, works by recognizing toxic RNA repeats and destroying the garbled gene transcript.

Gene therapy cassettes improved for muscular dystrophy
Experimental gene therapy cassettes for Duchenne muscular dystrophy have been modified to deliver better performance.

Discovery points to innovative new way to treat Duchenne muscular dystrophy
Researchers at The Ottawa Hospital and the University of Ottawa have discovered a new way to treat the loss of muscle function caused by Duchenne muscular dystrophy in animal models of the disease.

Extracellular RNA in urine may provide useful biomarkers for muscular dystrophy
Massachusetts General Hospital researchers have found that extracellular RNA in urine may be a source of biomarkers for the two most common forms of muscular dystrophy, noninvasively providing information about whether therapeutic drugs are having the desired effects on a molecular level.

Tamoxifen and raloxifene slow down the progression of muscular dystrophy
Steroids are currently the only available treatment to reduce the repetitive cycles of inflammation and disease progression associated with functional deterioration in patients with muscular dystrophy (MD).

Designed proteins to treat muscular dystrophy
The cell scaffolding holds muscle fibers together and protects them from damage.

Gene-editing alternative corrects Duchenne muscular dystrophy
Using the new gene-editing enzyme CRISPR-Cpf1, researchers at UT Southwestern Medical Center have successfully corrected Duchenne muscular dystrophy in human cells and mice in the lab.

GW researcher finds genetic cause of new type of muscular dystrophy
George Washington University & St. George's University of London research, published in The American Journal of Human Genetics, outlines a newly discovered genetic mutation associated with short stature, muscle weakness, intellectual disability, and cataracts, leading researchers to believe this is a new type of congenital muscular dystrophy.

Read More: Muscular Dystrophy News and Muscular Dystrophy Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.