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MDA Awards Venture Philanthropy Funding to Dr. Rachelle Crosbie to Develop a Novel Membrane-Stabilizing Drug for Duchenne Muscular Dystrophy

NEW YORK, July 16, 2019 /PRNewswire/ -- The Muscular Dystrophy Association (MDA) has awarded MDA Venture Philanthropy (MVP) funding totaling $389,463 over two years to Rachelle H. Crosbie, PhD, professor and chair of Integrative Biology and Physiology at the University of California, Los Angeles. The award will support the development of a small molecule drug that increases expression of sarcospan, a protein that may help to prevent the muscle damage that occurs in Duchenne muscular dystrophy (DMD). Currently, there are only two FDA-approved therapies to treat DMD.

MVP is MDA's drug development program, which is exclusively focused on funding the discovery and clinical application of treatments and cures for neuromuscular disorders. MVP evaluates and makes targeted investments in companies and academics developing therapeutics.

"Dr. Crosbie's team has identified sarcospan as a promising new drug target for Duchenne," says MDA President and CEO Lynn O'Connor Vos. "MDA is pleased to continue to support this successful line of research as her team now initiates a program to develop a novel therapy."

Sarcospan as therapeutic target

DMD is a genetic neuromuscular disease caused by mutations in the gene that makes dystrophin, a protein that is critical for maintaining the structural integrity of skeletal and cardiac muscle cells. When dystrophin is absent, muscle cells are much more susceptible to becoming damaged during use. Following repeated bouts of cellular damage, dystrophic muscle will eventually begin to degenerate and a person's function will progressively decline.

As a postdoctoral fellow with Kevin P. Campbell, PhD, at the Howard Hughes Medical Institute and the University of Iowa Carver College of Medicine, Dr. Crosbie identified a protein called sarcospan that may improve the structural integrity of dystrophic muscle in DMD. This initial discovery was funded by the Robert G. Sampson Neuromuscular Disease Research Award for postdoctoral training from MDA.

Sarcospan is naturally present in muscle, but Dr. Crosbie's laboratory showed that increasing its amount can convey a protective effect on skeletal and cardiac muscle in mice with muscular dystrophy. Her team has recently identified a set of small molecules that increase the levels of sarcospan, and with support from the MVP award, she will chemically optimize these lead compounds and test them in DMD mice and DMD human cells. Cynthia Shu, the graduate student in Dr. Crosbie's lab who performed the high-throughput screen to identify the sarcospan-enhancing compounds, was motivated to pursue the project after her family was personally affected by muscular dystrophy. If successful, this work may lead to the development of a novel drug that could slow the loss of function in limb muscles, respiratory muscles, and heart.

"We hope to identify a pre-clinical candidate that will treat DMD by boosting sarcospan levels," Dr. Crosbie says. "We also want to learn more about how our lead compounds target sarcospan in muscle cells so we can design better, more effective drugs."

Dr. Crosbie has received numerous funding awards from MDA, which have contributed to her current project. "The MDA has supported our research on sarcospan for over two decades, starting with my postdoctoral fellowship in 1996," she says. "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. It is exciting to be at this stage of developing drugs that enhance sarcospan."

About Duchenne muscular dystrophy

DMD occurs in 1 in every 3,500 to 5,000 males born worldwide. The disease primarily affects boys, but in rare cases it can affect girls. Onset of symptoms occurs in early childhood, usually between ages 3 and 5. Muscle weakness can begin as early as age 3, first affecting the muscles of the hips, pelvic area, thighs, and shoulders, and later the skeletal (voluntary) muscles in the arms, legs, and trunk. The calves often are enlarged. By the early teens, the heart and respiratory muscles also are affected.

Since its inception, MDA has invested more than $218 million in research for DMD and Becker muscular dystrophy (BMD).

About the Muscular Dystrophy Association

MDA is committed to transforming the lives of people affected by muscular dystrophy, ALS, and related neuromuscular diseases. We do this through innovations in science and innovations in care. As the largest source of funding for neuromuscular disease research outside of the federal government, MDA has committed more than $1 billion since our inception to accelerate the discovery of therapies and cures. Research we have supported is directly linked to approved, life-changing therapies across multiple neuromuscular diseases. We support the largest network of multidisciplinary clinics providing best-in-class care at more than 150 of the nation's top medical institutions, and each year thousands of children and young adults learn vital life skills and gain independence at MDA Summer Camp and through recreational programs. For more information visit mda.org.

SOURCE: Muscular Dystrophy Association