Discovery Could Lead to Better Treatments for Duchenne Muscular Dystrophy / ScienceDaily

In collaboration with scientists across the country, FSU researchers have discovered that increasing the levels of sarcospan protein improves heart function by strengthening the membranes of heart cells, which become weak in patients with DMD.

Their conclusions were published in the journal JCI Insight.

The disease, which usually affects young boys, is caused by a mutation that prevents the body from producing dystrophin, a protein essential for the health of skeletal, respiratory and cardiac muscles. Advances in the treatment of certain types of DMD-related muscle degradation have helped extend the life of patients. However, as DMD patients age, their cardiac function decreases considerably.

"Patients usually live up to 20 or 30 years," said lead author Michelle Parvatiyar, badistant professor in the Department of Nutrition, Food and Exercise Sciences at the College of human sciences of the FSU. "There have been significant improvements in respiratory care, which a majority of patients succumbed to, now in their twenties or thirties they often succumb to cardiomyopathy, the heart is functioning with a major component of the cell. Missing, over time, she uses it. "

This study was part of the ongoing efforts of Rachelle H. Crosbie, a biologist at UCLA, the corresponding author of the study, who had previously identified sarcospan as a protein likely to enhance the mechanical support of membranes skeletal cells devoid of dystrophin. His discovery stimulated DMD researchers and confirmed the potential of sarcospan as an effective tool in the fight against the disease.

"But no one had really looked at the effect that could have the increase in the level of this protein on the heart," Parvatiyar said.

Using a unique mouse model with a shortage of dystrophin, Parvatiyar and his collaborators did just that.

In their study, the team found that although it is not an identical substitute for dystrophin, overexpression of sarcospan in heart cells appears to help stabilize cell membranes. The researchers found that even under stress, overexpression of sarcospan could improve membrane defect in dystrophin-deficient cells.

"Sarcospan is not quite the work of dystrophin, but it acts as a binder to stabilize the membrane and keep the protein complexes together when dystrophin is lacking," Parvatiyar explained, explaining a concept developed by Crosbie.

Cardiac measurements have confirmed that sarcospan protects the cell membrane even when the heart is under stress. Co-author of this study and Associate Professor Josef Pinto of the USF College of Medicine conducted the measurements, alongside Karissa Dieseldorff Jones, graduate student of the USF, and Rosemeire Takeuchi Kanashiro, badistant Research at the Miller School of Medicine.

In addition to serving as a sort of stabilizing glue, the researchers said that sarcospan could also act as a scaffold that supports other proteins essential to the cell membrane. This function could allow sarcospan to carry mini-versions of dystrophin – which, in its normal state, has a long and difficult-to-handle genetic code – at the edges of cardiac cells, where they could strengthen fragile membranes.

"The idea is that you can administer sarcospan and dystrophin at the same time, and that sarcospan can facilitate the localization of mini-dystrophin on the cell membrane and help keep these complexes in place," Parvatiyar said. .

According to Parvatiyar, the two possible Sarcospan functions could complement existing DMD treatments or lead to new therapies that strengthen the membranes of weakened heart cells and improve the quality of life for people with DMD.

In his previous position at UCLA, Parvatiyar has had frequent interactions with DMD patients and their families. She said that these interactions and the steadfast hope she faces in people with DMD continue to push her and her colleagues to find new ways to fight this debilitating disease.

"It was the first time in my life that someone would come to thank me and thank me for my work," she said. "Sometimes you feel withdrawn from the lab day after day, you see gradual progress, but seeing people who really need help is motivating, and their positivity is incredibly inspiring."

Researchers from UCLA, the University of Miami, SUNY Binghamton University, and the University of Washington contributed to this study. Funding was provided by the National Institutes of Health, the Duchenne Muscular Dystrophy Center of the UCLA-CureDuchenne Postdoctoral Fellowship and the American Heart Association.