In Lab Research, Scientists Slow Progression of a Fatal Form of Muscular Dystrophy
In a paper published in the Nature journal Scientific Reports, Saint Louis University researchers report that a new drug reduces fibrosis (scarring)
and prevents loss of muscle function in an animal model of Duchenne muscular dystrophy
(DMD), providing a promising approach in designing new medications for those suffering
DMD is a fatal form of a muscle wasting disorder that affects one out of every 5,000
to 10,000 boys. The illness is caused by mutations in a gene on the X chromosome.
With treatment, those with DMD have an average lifespan of around 25 years. Boys with
the illness typically need to use a wheelchair by age 12 and require mechanical ventilation
to help with breathing. Many eventually suffer cardiac or respiratory failure.
Thomas Burris, Ph.D., chair of pharmacology and physiology at Saint Louis University
and Colin Flaveny, Ph.D., assistant professor of pharmacology and physiology at SLU,
study natural hormones that regulate nuclear receptors. By understanding how the body’s
natural hormones operate, they aim to develop synthetic compounds to target these
receptors in order to create drugs to treat diseases.
In the course of this work, Burris and Flaveny have explored the roles of the nuclear
receptor REV-ERB, which regulates key processes in the body, from sleep to cholesterol,
and, most recently, muscle regeneration.
“Recently, we found that REV-ERB appears to play unique roles for each stages of
muscle tissue development,” Flaveny said.
Muscle stem cells which help replace damaged muscle tissue produce myoblasts that
will either reproduce (proliferate) or form muscle tissue (differentiate).
A decline in expression of REV-ERB leads to myoblast differentiation. Conversely,
an increase in REV-ERB expression is involved in the regulation of mitochondrial and
metabolic function in fully differentiated skeletal muscle.
The team showed that REV-ERB is a regulator of muscle differentiation, and that a
drug that inhibits this receptor, called SR8278, stimulates muscle regeneration after
Following up on these promising results, they decided to explore whether the drug
SR8278 could slow the progression of muscular dystrophy in an animal model.
DMD patients experience ongoing cycles of muscle destruction and regeneration that
promote inflammation, fibrosis (scarring), and the loss of skeletal and cardiac muscle
Validating their theory, the research team discovered that SR8278 increased lean
mass and muscle function and decreased muscle fibrosis and muscle protein degradation
“These results suggest that REV-ERB is a potent target for the treatment of DMD,”
Burris said. “This is an encouraging finding as we search for better treatments for
those with this debilitating illness.”
Other researchers on the project include Ryan D. Welch, Cyrielle Billon and Aurore-Cecile
The study was supported by a grant from the National Institutes of Health (grant
Established in 1836, Saint Louis University School of Medicine has the distinction
of awarding the first medical degree west of the Mississippi River. The school educates
physicians and biomedical scientists, conducts medical research, and provides health
care on a local, national and international level. Research at the school seeks new
cures and treatments in five key areas: cancer, liver disease, heart/lung disease,
aging and brain disease, and infectious diseases.