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March 28, 2008

Myostatin inhibitor update: Boosting follistatin may be better

Wyeth is not stopping developement of drug MYO-029 for blocking myostatin. They foudnd that MYO-029 was safe but that it was not very good at blocking myostatin or boosting muscle growth. They and other companies are working on more powerful and hopefully effective versions.

Two sets of experiments investigating the effects of interfering with myostatin, a protein that limits muscle growth, have shown that this approach may have to be individualized with respect to different types and stages of muscular dystrophy, and that some myostatin suppression strategies may be better than others. Boosting follistatin not only suppresses myostatin but also affects various cell signaling pathways and reduces inflammation. I had previously covered the follistatin gene therapy where it increased muscle size by four times for mice, but that did not describe the differences between the different methods. I have also had extensive coverage of myostatin inhibitors and the safer and more effective increase in muscle mass over high dosage steroids that they represent. Safely increasing muscle mass will not be good for making people stronger it can also help with fat reduction and control (muscle burns more calories) and can help with the health of more frail people (stronger people can stay more mobile and are able to tolerate falls better.

Investigators injected genes for the protein follistatin inside an adeno-associated viral shell into upper and lower leg muscles in 3-week old mice with DMD. Follistatin is known to inhibit myostatin activity. The mice, divided into high-dose and low-dose treatment groups and an untreated (control) group, were then observed for five months.

The mice treated with follistatin genes developed larger bodies and larger, heavier muscles, with the high-dose group showing the greatest effects. Follistatin was detected in the bloodstream of low- and high-dose-treated mice, and it affected muscles far from the injection sites.

The investigators observed an increase in the size of muscle fibers in mice receiving the gene therapy but not in fiber numbers.

Both groups of treated mice showed reduced levels of creatine kinase, indicating less leakiness of muscle-fiber membranes compared to control mice. The researchers speculate that the treated fibers became less susceptible to damage.

The investigators then injected 7-month-old DMD-affected mice with follistatin genes in viral shells. These older mice showed increases in strength about two months after the injections, which persisted for the more than 18 months during which the mice were evaluated.

At the end of the study, the treated mice had substantially fewer groups of dead muscle fibers, fewer inflammatory cells in their muscles, and less scar tissue than did untreated mice, and their muscle fibers were larger in diameter than those of the control group.

The improvements were sustained and well tolerated over more than two years.

Boosting follistatin not only suppresses myostatin but also affects various cell signaling pathways and reduces inflammation.


1 comments:

Sigma said...

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http://www.intelligencerealm.com/aisystem/news.php