A New Approach to Myostatin-Related Muscle Growth
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Blocking myostatin has been shown to boost muscle growth and regeneration in various species. There are even a few natural human myostatin mutants, but that is a rare genetic occurrence. For some years now researchers have been investigating means to manipulate myostatin levels and related signaling as a therapy for age-related loss of muscle mass and strength, as well as for various other medical conditions in which wasting of muscles plays a role. This, like many forms of modern medical research, aims to produce a form of compensatory change, potentially beneficial but in no way addressing root causes to prevent progression of the underlying condition.

Researchers here have moved on past myostatin and further down the chain of signals and molecular mechanisms to find a novel place to intervene in order to boost muscle growth in mice and humans. So far results are promising: if this treatment turns out to produce few to no side-effects, it is the sort of thing that everyone could benefit from. That said, again, it doesn't address root causes of degenerative muscle loss with aging - something that needs to be accomplished in order to reliably and most effectively extend healthy life.

New Compound Could Reverse Loss of Muscle Mass in Cancer and Other Diseases

The new compound (BYM338) acts to prevent muscle wasting by blocking a receptor that engages a cellular signaling system that exists to put the brakes on muscle development when appropriate. But sometimes those brakes are activated inappropriately, or are stuck on.

A variety of signals can activate the receptor. Prior to development of BYM338, compounds developed to block these molecules were blunt instruments, either trapping all incoming signals (which stimulated muscle growth but also caused harmful side effects) or blocking just a single receptor activator (providing only tepid growth stimulation.) BYM338 was designed to be in the Goldilocks zone (just right.)

In the study the compound boosted muscle mass 25 to 50 percent and increased strength in animal models. Those gains were significantly superior to those of compounds that blocked a single receptor activator. Clinical trials are currently underway. Preliminary data on the antibody was promising enough to have it designated a breakthrough therapy by the US Food and Drug Administration for sporadic inclusion body myositis, a rare muscle wasting disease with no approved therapies.

Here is a link to the paper - the PDF format full version is also presently available if you'd like to wade in to the details.

An Antibody Blocking Activin type II Receptors Induces Strong Skeletal Muscle Hypertrophy and Protects from Atrophy

The myostatin/Activin type II receptor (ActRII) pathway has been identified as critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the Activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass.

We have developed a novel, human anti-ActRII antibody ("Bimagrumab", aka BYM338) to prevent binding of ligands to the receptors, and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts, and counteracts the inhibition of differentiation induced by myostatin or Activin A.

BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin as detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin-mutant mice, further confirming a beneficial effect on muscle growth through blockade of ActRII ligands beyond myostatin inhibition alone.

Comments

A very important development. Inhibiting the unfortunate rise in myostatin may prevent diabetes, obesity, mitochondrial decay and their very unfortunate consequences (cancer, dementia, heart disease, hypertension...) For example, see the (cached item -

"Ways to prevent obesity, diabetes identified"

http://webcache.googleusercontent.com/search?q=cache:DtJ53Y0pLUIJ:articles.timesofindia.indiatimes.com/2012-12-20/health/35932770_1_muscle-loss-muscle-cell-obesity-and-diabetes

Posted by: Lou Pagnucco at December 23, 2013 9:33 PM

does if also block gdf-11 which is meant to have wonderful ageing benefits

Posted by: Leon Horsnell at January 21, 2014 1:33 AM
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