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Muscle fibrosis reversed in new study

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Overuse injuries — such as muscle strains, tennis elbow and rotator cuff tears — are caused by episodes of repeated stress without the body having a chance to fully rest and recover.

High-force, high-repetition movements create microinjuries in muscle fibres, and without proper rest these microinjuries progress to fibrosis — the replacement of muscle tissue with connective tissue. Fibrosis ultimately weakens the muscles and can put pressure on nerves, causing pain, explains Temple University in Philadelphia.

The condition has long been thought to be irreversible, but new research by scientists at the Lewis Katz School of Medicine (LKSOM) at Temple shows that it may be possible to undo the damage caused by fibrosis and, in the process, restore muscle strength.

For the study, the researchers trained rats to complete a task in a high-force, high-repetition manner for a reward. After 18 weeks, the animals trained on the task developed muscle fibrosis characteristic of overuse injury.

The animals were then divided into three groups: one that received no treatment, one that received an inactive “sham” treatment, and one that received a drug known as FG-3019. This drug, which works by blocking the activity of a protein called CCN2, was recently approved by the US Food and Drug Administration for the treatment of Duchenne muscular dystrophy.

The treatment period lasted six weeks, during which all animals were given a rest from the high-force, high-repetition task.

Following the six weeks of rest, muscle tissue analysis showed that untreated animals and sham-treated animals had elevated muscle levels of fibrosis-related proteins, including collagen and CCN2, which promotes the growth of connective tissue. By contrast, in FG-3019-treated animals, CCN2 and collagen levels were similar to the levels seen in control rats that were not trained to perform the repetitive task. Fibrotic damage was also reversed in animals given FG-3019, and these animals showed significant improvements in grip and other tests of muscle strength, the university reported.

“FG-3019 is already in clinical trials for other diseases involving fibrosis, including pulmonary fibrosis and kidney fibrosis,” said Mary F. Barbe, PhD, Professor of Anatomy and Cell Biology and Professor in the Department of Physical Therapy at LKSOM. “Our work adds to the relevance of this drug in treating fibrotic diseases, with the novel application for muscle fibrosis associated with overuse injury.”