The Muscular Dystrophy Association (MDA) awarded $389,000 in funding to a researcher from University of California, Los Angeles (UCLA) to support the development of a small molecule that holds promise for preventing muscle damage in Duchenne muscular dystrophy (DMD). The molecule raises levels of a muscle protein called sarcospan, an important regulator in muscle cells.
The funding, which will run for two years, was awarded to Rachelle H. Crosbie, PhD, professor and chair of integrative biology and physiology at UCLA.
“Dr. Crosbie’s team has identified sarcospan as a promising new drug target for Duchenne,” Lynn O’Connor Vos, MDA president and CEO said in a press release. “MDA is pleased to continue to support this successful line of research as her team now initiates a program to develop a novel therapy.”
As a postdoctoral fellow with leading MD researcher Kevin P. Campbell, Crosbie identified the sarcospan protein. Naturally present in muscle cells, sarcospan associates with a group of proteins that also includes dystrophin — the defective protein in people with DMD.
Dystrophin is primarily found in muscles used for movement, known as the skeletal muscles, and in the heart muscle, where it works together with other proteins — including sarcospan — to strengthen muscle fibers and protect them from injury.
People with DMD lack normal dystrophin, which makes their muscle fibers prone to potential damage every time a muscle is used. Following repeated rounds of cell damage, muscles will begin to degenerate and a person’s function will progressively decline.
Crosbie and colleagues from her lab showed that increasing the levels of sarcospan helps stabilize the membrane of muscle cells, improving the structural integrity of the dystrophic muscle. This could be a way to oppose muscle deterioration, the researchers say.
The scientists did preliminary studies in mouse models, proving that overexpression of sarcospan holds therapeutic potential, effectively protects against skeletal muscle injury and pulmonary dysfunction. It also protects against heart muscle disease (cardiomyopathy) associated with DMD.
The team has recently identified a set of small molecules that are able to increase the levels of sarcospan. The MDA’s award will now be used to support optimizing these compounds and testing them in DMD mice, and DMD human cells.
Cynthia Shu, the graduate student who performed the high-throughput screen to identify the compounds, began her work after her family was personally affected by muscular dystrophy.
If successful, this research may lead to the development of a new therapy that could slow the loss of function in limb and breathing muscles, and in the heart.
“We hope to identify a pre-clinical candidate that will treat DMD by boosting sarcospan levels,” Crosbie said. “We also want to learn more about how our lead compounds target sarcospan in muscle cells so we can design better, more effective drugs.”
Crosbie’s award is funded through the MDA Venture Philanthropy (MVP), the association’s drug development program. The initiative is intended to provide funding exclusively to companies or academics engaged in the discovery and clinical application of treatments and cures for neuromuscular diseases.
“The MDA has supported our research on sarcospan for over two decades, starting with my postdoctoral fellowship in 1996,” Crosbie said.
“It has been a long road of basic science research to establish sarcospan as a target for DMD, and the MDA has been instrumental during this journey,” she said. “It is exciting to be at this stage of developing drugs that enhance sarcospan.”