Raising Levels of Protein, Sarcospan, Seen to Benefit Cardiac Muscles in Mouse Model of DMD

Increasing the amount of a protein called sarcospan may help to protect against heart failure in children with Duchenne muscular dystrophy (DMD), a study in mice suggests.

The study, “Stabilization of the cardiac sarcolemma by sarcospan rescues DMD-associated cardiomyopathy,” was published in the journal JCI Insight.

Despite significant advances in caring for people with DMD, heart health remains a major problem, especially as these children age.

“There have been important improvements in respiratory care, which used to be what a majority of [DMD] patients would succumb to,” Michelle Parvatiyar, PhD, an assistant professor at Florida State University and the study’s co-author, said in a press release. “Now, in their 20s and 30s, they’re often succumbing to cardiomyopathy.”

DMD is caused by a lack of the protein dystrophin, which is critical for the working of muscles in the body, including cardiac muscles.

“The heart is functioning with a major component of the cell membrane missing,” Parvatiyar said. “Over time, it wears out.”

Previous research has demonstrated that the small protein sarcospan, which normally interacts with dystrophin, could improve mechanical support in skeletal muscles lacking dystrophin — compensating somewhat for the missing protein.

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“But,” Parvatiyar said, “nobody had really looked at how increasing the levels of this protein might affect the heart.”

The researchers used a viral vector to increase the expression of sarcospan in mdx mice (a mouse model of DMD), both with mild and severe disease. They then assessed the mice’s hearts to see how well they functioned. Namely, they looked to see if heart tissue appeared healthy under a microscope and through echocardiography, a test that allows researchers to visualize the heart and its valves to see how well they work.

Increased sarcospan levels did indeed improve heart health. The effect wasn’t so strong that the mice appeared otherwise healthy, but it was still a significant improvement — and an improvement even when the hearts were put under stress.

The reason for this effect appears to be sarcospan’s ability to help other proteins in the membranes of heart cells line up properly; sarcospan acts as a sort of adhesive or scaffold, helping the membrane be more durable and stable, so as to delay progression toward heart failure.

“Sarcospan doesn’t quite do the job of dystrophin, but it acts as a glue to stabilize the membrane and hold protein complexes together when dystrophin is lacking,” Parvatiyar said.

Therapy approaches centered around this understanding of sarcospan may one day augment current treatments or lead to entirely new therapies, but more research is needed before such an approach might be used with children.

“We demonstrate that correcting membrane permeability defects improves cardiac function in both mild and severe DMD models,” the study concludes. “Furthermore, we show that SSPN [sarcospan] overexpression is able to ameliorate cardiac function and membrane integrity without upregulating utrophin [an analog of dystrophin], therefore showing promise in alleviating both skeletal and cardiac muscle dysfunction in human disease.”