Shortened Telomeres a Possible Factor in Muscle Weakness, Atrophy of Muscular Dystrophy

Findings may provide new treatment options for Duchenne muscular dystrophy.

Shortened telomeres in muscle stem cells is a factor in weakening and atrophy of muscles in young patients with Duchenne muscular dystrophy (DMD).

In a study published in Stem Cell Reports, investigators developed a novel method that measured stem cell telomeres. The technique was based on the existing method called fluorescence in situ hybridization (FISH).

The findings showed telomeres in the muscle stem cells of teenage boys with DMD are abnormally short, as well as in young mice with DMD.

“We found that in boys with DMD, the telomeres are so short that the muscle stem cells are probably exhausted,” said senior author Foteini Mourkioti, PhD. “Due to the DMD, their muscle stem cells are constantly repairing themselves, which means the telomeres are getting shorter at an accelerated rate, much earlier in life.

“Future therapies that prevent telomere loss and keep muscle stem cells viable might be able to slow the progress of disease and boost muscle regeneration in the patients.”

Muscle stem cells could regenerate loss of muscle and, as a result, slow or even stop the dystrophy; however, scientists suspect this continuous cycle of muscle damage and repair erodes the regenerative capacities of muscle stem cells in patients with DMD by shortening telomeres and inducing senescence.

“The problem with trying to identify what is happening in DMD muscle stem cells is that we’ve lacked sufficient tools for measuring telomere length in these stem cells,” Mourkioti said.

Based off FISH, the investigators developed a novel stem cell telomere-measuring method. The new FISH-based method uses a fluorescent probe that is designed to stick specifically to the telomeres, and is made of a short sequence of DNA building blocks.

The authors noted that the technique can be used with both electronic imaging equipment and a microscope to measure the telomeres length within each stem cell.

Originally, the technique was used to demonstrate that the telomeres of muscle stem cells are approximately the same length in healthy lab mice. In comparison, muscles stem cells on average had abnormally shortened telomeres in young mice with severe DMD-like disorder and several teenage patients diagnosed as having DMD.

The study findings suggest that gene therapy and other treatments in development for muscular dystrophies may be more beneficial if administered before the muscle stem cells lose their ability to regenerate.

Additionally, future treatments could potentially block the shortening of telomeres in muscle stem cells to help slow or stop the disease.

“We are now looking for signaling pathways that affect telomere length in muscle stem cells, so that in principle we can develop drugs to block these pathways and maintain telomere length,” Mourkioti said. “Currently, very little is known about the factors that shorten or maintain telomeres.”

DMD and Becker muscular dystrophy affects 1 in every 7250 males aged 5 to 24 years, according to the CDC.