‘Limb Girdle’ MD Genetics Research Gets Boost from NIH Grant

Alysia Vrailas-Mortimer and her research team at Illinois State University have received a $435,000 grant from the National Institutes of Health (NIH) to continue unveiling the genetics of muscular dystrophy, specifically “limb girdle” muscular dystrophy.

The team studies this special form of muscular dystrophy, which attacks muscles around the shoulders and hips. Symptoms of patients suffering from limb girdle muscular dystrophy usually worsen with aging and eventually stop walking.

From the 31 genes associated with limb girdle muscular dystrophy, Mortimer’s team focused in a particular gene known to regulate life span and aging; it is called p38. This gene has been linked to other aging-associated diseases such as Alzheimer’s and Parkinson’s.

The common fruit fly was used by the team to study the processes mediated by the p38 gene. Mortimer said she used the fly as a model because it is much simpler than humans, but shares the disease-causing genes. “About 75 percent of all genes that cause diseases in humans have an equivalent in the fly,” Mortimer, whose lab contains thousands of colonies of fruit flies, said in a news release. “Because the fly has such a simpler system, and we know its genome, we can understand how it might contribute to a disease in a very basic way.”

During the past few years, the research team compiled evidence showing that p38 may regulate other genes involved in muscular dystrophy. Moreover, they know that p38 helps to clear up damaged proteins that accumulate in the muscle cells, a process known as autophagy. Autophagy is a physiological process that degrades protein aggregates and is vital for functional skeletal muscle.

“Think of it like the tires in your car. When they wear down, they need to be replaced. The cells and proteins in your body are the same,” Mortimer explained.

The researchers believe that malfunction of p38 leads to protein aggregates that are “toxic garbage” for the muscle cells, resulting in locomotor disability. The team also is interested in studying the relationship between p38 and other limb girdle disease-associated genes. With NIH funding the team can pursue its investigation and further understand how p38 cellular function can be targeted to prevent muscular dystrophy.