Gene found to activate muscle stem cells in mice with muscular dystrophy

Julie Saba grew up with a father who was a muscle biochemist and, out of rebellion, she swore she’d never go into research, especially muscle research. She was just going to be a doctor. A doctor who, years later, did run a research lab, but in cancer.

Then, when studying a particularly interesting gene involved in cancer biology, she discovered that fruit flies lacking the gene couldn’t fly. Their flight muscles didn’t work properly.

“I felt like nature pointed me in this direction and I had to follow this lead,” Saba said.

In a May 14 paper published in Public Library of Science ONE she described the results of following that lead. She discovered how the protein, called S1P, triggers muscle stem cells called satellite cells to repair muscle damage. Saba, who is senior scientist at Children's Hospital Oakland Research Institute (CHORI), was working with a CIRM training grant recipient Kenneth Loh. Loh is first author on the paper.

Saba’s father, the muscle biochemist, is reportedly thrilled that his daughter is taking on the family business.

A press release describes how this serendipitous work could help people with forms of muscular dystrophy:

"These findings are important especially for certain muscle diseases or "myopathies" that can affect children," states Dr. Saba. The most common and one of the most severe myopathies is Duchenne Muscular Dystrophy, a disease that affects young boys and often leads to death from respiratory and heart failure in a patient's twenties. Although patients with Duchenne Muscular Dystrophy start out life with enough satellite cells to repair the patients' degenerating muscles, over time the satellite cells fail to keep up with the rate of muscle degeneration. "We found that mdx mice, which have a disease similar to Duchenne Muscular Dystrophy, are deficient in S1P. We were able to increase the S1P levels in the mice using a drug that blocks S1P breakdown. This treatment increased the number of satellite cells in the muscles and improved the efficiency of muscle regeneration after injury."

I really like this study in part because it is a great example of the twists and turns of research. Saba says half of her cancer lab is now dedicated to muscle research.

On our website we have a list of CIRM awards focusing on muscular dystrophy. These range from very basic awards, with researchers trying to better understand the disease, to awards in which researchers are trying to turn discoveries into new therapies for this devastating disease.

A.A.