© 2025 Texas Public Radio
Real. Reliable. Texas Public Radio.
Play Live Radio
Next Up:
0:00
0:00
0:00 0:00
Available On Air Stations

Science & Medicine: Why are neurodevelopmental disorders common in Duchenne muscular dystrophy?

Ways To Subscribe
Roberto Martinez
/
TPR

Duchenne muscular dystrophy (DMD) is a devastating genetic disease that is generally diagnosed at around two or three years of age when children typically begin crawling or walking. These milestones are difficult and may be delayed for children with DMD. Most will require a wheelchair between the ages of twelve and fourteen and many will die in their twenties.

DMD is inherited on the X chromosome, so it is far more likely to affect those with only one X chromosome, typically boys. Girls usually have a second X chromosome that can compensate for a mutation on the first. Up to 20,000 people are living with this condition in the United States.

The genetic variation in DMD causes the deficiency or absence of a protein that protects muscles from damage, called dystrophin, leading to progressive muscular deterioration. Dystrophin also protects the heart muscle and the diaphragm, and the lack of it leads to heart or respiratory failure.

Last year, however, the Food and Drug Administration approved a gene therapy for DMD that uses a virus to produce a version of dystrophin in muscles. This can slow deterioration and offer hope for longer lives in people with DMD.

Now, families are looking for ways to further improve the quality of those lives, according to Jason Pugh, Ph.D. He's a neuroscientist and an associate professor in the Department of Cellular and Integrative Physiology at UT Health San Antonio. "As we get closer to treating the muscle symptoms of this disease, parents are really looking for information and research on what is happening in the brain," Pugh said.

Jason Pugh, PhD Associate Professor Department of Cellular and Integrative Physiology The University of Texas Health Science Center at San Antonio
Teves, Eileen
Jason Pugh, PhD
Associate Professor
Department of Cellular and Integrative Physiology
The University of Texas Health Science Center at San Antonio

That has been the focus of Pugh's work for nearly a decade. Back then, he was studying Purkinje cells, a type of neuron in the cerebellum that plays a crucial role in motor coordination. He wondered if they might play a role in muscular dystrophy. Turns out, Purkinje cells have the highest concentration of dystrophin expression in the brain.

What does that mean for the brains of kids with Duchenne muscular dystrophy? Pugh says kids with DMD often have cognitive dysfunction alongside muscle deterioration.

“Those typically involve deficits in working memory and verbal memory,” Pugh said. “Many of these patients are also diagnosed with neurodevelopmental disorders. Autism spectrum disorder, ADHD, and OCD are much more prevalent in the population of boys with muscular dystrophy.”

Pugh is trying to figure out if dystrophin deficiency has a part to play in this, too. In his lab, they’re using a mouse model to try to answer a series of questions about the protein.

“What is the function of dystrophin in neurons? How does loss of dystrophin change the function of neurons?” Pugh asked. “Can we find ways of restoring neuronal function in the absence of dystrophin?”

If you could restore function in Purkinje cells so that they express dystrophin in the brain, would that restore synaptic function and reduce cognitive dysfunction? Or does dystrophin need to be present during earlier, critical periods of development?

Very little research has been done on the impact of muscular dystrophy on the brain. Pugh is truly a trailblazer in the field, and for a long time, it was difficult to find support for his work, he said. After all, the people he was seeking to help didn’t live very long.

“One of the first grants I submitted on this, the reviewers came back and said, ‘Why should we care about what's happening in the brain when these children are dying from the muscle symptoms?’” Pugh recalled. “But I think we're now at the point where we've made so much progress in treating muscle symptoms, it's time to understand what's happening in the brain.”

Parents frequently reach out to him, Pugh added, wanting to know what he’s learned and what he hopes to learn.

“I think that's the future of research in muscular dystrophy,” he said, “understanding what's happening in the brain and other organ systems.”

Answering these questions could also help scientists better understand the underlying mechanisms of neurodevelopmental diseases like autism and ADHD in the general population, which could lead to more effective treatments for those with and without DMD.

Science & Medicine is a collaboration between TPR and The University of Texas Health Science Center at San Antonio that explores how scientific discovery in San Antonio advances the way medicine is practiced everywhere.