UC scientist studies role of protein in skeletal muscle disorders

A University of Cincinnati researcher has received a five-year $2.3 million grant to study the role a protein in muscles plays in the development of a rare disease. The grant is from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

The condition, called distal arthrogryposis, is a skeletal muscle disorder characterized by the presence of joint contractures, or a tightening or shortening of the joint causing a deformity, at various parts of the body, particularly in the furthest extremities, explains Sakthivel Sadayappan, PhD, professor in the UC Division of Cardiovascular Health and Disease. The condition affects one in 3,000 live births and leads to increased connective tissue formation around the joints in a way that immobilizes muscle movement leading to deformities in children.

“The goal of our current research is to define the physiologic mechanisms underlining how mutations in slow skeletal myosin binding protein-C seen in animal models leads to muscle dysfunction and contractures,” says Sadayappan. “We hypothesize that the slow skeletal protein is a key regulator of striated skeletal muscle formation and function.”

Experiments will look at defining the role of myosin binding protein-C in regulating skeletal muscle function in four unique animal models. “Understanding the molecular mechanisms that underlie a reduced contractility in muscle disease should help us identify novel therapeutic targets to improve muscle function in individuals afflicted with distal arthrogryposis,” says Sadayappan.

Featured image of Sakthivel Sadayappan, PhD, in his laboratory at the UC College of Medicine. Photo by Colleen Kelley/UC Creative + Brand.

Sadayappan’s work is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases grant 1R01AR078001-01.