Possible muscle disease therapeutic target found

The study of muscular system protein myostatin has been of great interest to researchers as a potential therapeutic target for people with muscular disorders. Although much is known about how myostatin affects muscle growth, there has been disagreement about what types of muscle cells it acts upon. New research from a team including Carnegie's Chen-Ming Fan and Christoph Lepper narrows down the field to one likely type of cell. Their work is published the week of August 6 by Proceedings of the National Academy of Sciences.

Myostatin is known to inhibit muscle growth and its function is common in many mammals, including cows, sheep, dogs, humans, and mice. lacking in myostatin have muscle mass that is almost double that of normal mice. This property is what makes it an attractive potential . By inhibiting myostatin a drug could, in theory, promote muscle growth, even in a person with a muscular disease.

There has been considerable debate about which types of are targeted by myostatin: fibrous muscle cells called myofibers, or muscle stem cells called . The satellite cells are activated by muscular injury, begin to divide, and fuse to myofibers. Some studies seem to indicate myostatin targets satellite cells, others indicate myofibers.

The research team, co-led by Fan and Se-Jin Lee, who is a former Carnegie Staff Associate and currently at Johns Hopkins University Medical School, used a variety of techniques—both genetic and pharmacological—and determined that the muscle growth caused by inhibiting myostatin does not significantly involve the incorporation of satellite cells into myofibers.

This finding has major implications for the possible use of myostatin as a clinical target. There are outstanding questions about how a drug designed to target myostatin would work in clinical conditions in which patient's satellite cells are depleted. For example, in diseases like muscular dystrophy, satellite cells are believed to compensate for degenerated muscle cells in the early stages of the disease, causing the pool of these stem cells to shrink over time. This work raises the possibility that these patients might still benefit from myostatin inhibitors.

"More work is needed to determine whether these findings are applicable to various clinical conditions, such as exercise, injury, and sarcopenia—degenerative loss of muscle mass associated with aging," Fan said. "However, our findings initially indicate that many different diseases affecting the muscular system could potentially be responsive to drugs that inhibit and thus promote muscle growth, without regard to the status of the muscle stem cell pool."

Related Stories

'Mighty mice' made mightier

Aug 29, 2007

The Johns Hopkins scientist who first showed that the absence of the protein myostatin leads to oversized muscles in mice and men has now found a second protein, follistatin, whose overproduction in mice lacking ...

New kind of mutation is reported

Jun 05, 2006

Belgium scientists say they have discovered a new kind of mutation that might be at the origin of many phenotypes in various species.

Researchers Shed Light on Muscle Growth Regulator

Jul 30, 2009

(PhysOrg.com) -- Research at the University of Cincinnati has led to the first published structure of myostatin, a protein that regulates muscle growth in animals, offering hope for major advances in the fight ...

Recommended for you

Unlocking the secrets of pulmonary hypertension

8 hours ago

A UAlberta team has discovered that a protein that plays a critical role in metabolism, the process by which the cell generates energy from foods, is important for the development of pulmonary hypertension, a deadly disease.

New molecule sneaks medicines across the blood/brain barrier

13 hours ago

Delivering life-saving drugs across the blood-brain barrier (BBB) might become a little easier thanks to a new report published in the November 2014 issue of The FASEB Journal. In the report, scientists describe an antibo ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.