Julio Vergara, professor of physiology at the University of California, Los Angeles, was awarded an MDA research grant totaling $300,000 over a period of three years to study the basis of central core disease (CCD).
CCD is an inherited muscle disease that causes poor muscle tone and weakness, susceptibility to heat-related illnesses, and a risk of malignant hyperthermia, a dangerous reaction to certain anesthetic drugs. One cause of CCD is a defect in a muscle protein called the type 1 ryanodine receptor, which regulates the releases of stored calcium in the muscle. This release of calcium is critical for normal muscle contraction.
Much remains to be understood about the connections between CCD and alterations in the ryanodine receptor, Vergara says. His work will pursue these connections in mice carrying the mutant gene.
“Our research aims to answer the following questions,” Vergara explains. “Why do mutated receptors predispose muscle fibers to triggering agents that lead to fulminant [sudden, rapid, severe] malignant hyperthermia episodes? And, how does dantrolene, a commonly used drug, prevent fulminant MH episodes?”
He will investigate these issues using a combination of state-of-the art optical and electrophysiological approaches in adult muscle fibers from animal models, and comparing calcium release among mice with different mutations in the receptor gene.
“The mice have become a great tool to investigate the molecular and pathophysiological alterations underlying the mysteriously intertwined malignant hyperthermia/CCD human pathology,” Vergara says.
Funding for this MDA grant began August 1, 2013.