Friday, May 16, 2008

ACE-031 (Muscle Growth)

ACE-031, the lead product in Acceleron’s muscle program, is being developed to treat diseases involving the loss of muscle mass, strength and function in diseases including muscular dystrophy, amyotrophic lateral sclerosis and cancer-related muscle loss. ACE-031 works by inhibiting myostatin and other negative regulators of muscle mass thereby freeing the body to rebuild muscle tissue.

Myostatin Limits the Production of Muscle

There are natural checks and balances in many processes in the human body, including the process that controls formation of muscle mass. Myostatin, also known as Growth Differentiation Factor-8 (GDF-8), works as a negative regulator of muscle mass, essentially limiting the body’s ability to add muscle. Over-expression of myostatin has been shown to cause a loss in muscle mass and strength, whereas inhibition of myostatin results in the selective increase in skeletal muscle mass and strength.

There are several examples in animals with genetic mutations that lead to low levels of myostatin, resulting in huge increases in muscle mass. For instance, the photo above shows the myostatin-deficient Belgian Blue breed of cattle, which despite being otherwise normal, have tremendously increased muscle mass.

ACE -031: A Decoy Myostatin Receptor

ACE-031 was specifically developed to inhibit myostatin and other negative regulators of muscle mass and strength. The reduction of myostatin would enable the body to add muscle mass to muscles weakened by disease. ACE-031 is a biotherapeutic based on the activin receptor type IIB (ActRIIB), which is the natural receptor for myostatin and other negative regulators of muscle mass. Acceleron scientists have engineered the product to combine the portion of ActRIIB that binds tightly to myostatin with a component of an antibody molecule that allows ACE-031 to circulate freely throughout the body.

Inhibiting the Inhibitor: Using ACE-031 to Grow New Muscle

ACE-031 acts as a decoy receptor and binds myostatin before it is able to bind with ActRIIB on the surface of muscle cells. Binding prevents myostatin signaling, thereby allowing normal muscle formation processes to occur, resulting in increased muscle mass and strength.

Recent studies with ACE-031 suggest that targeting myostatin may be a powerful way to increase muscle mass and improve physical function. In a range of animal models of muscle disease, including models of muscular dystrophy, amyotrophic lateral sclerosis, glucocorticoid-induced muscle loss and age-related muscle loss (sarcopenia), ACE-031 increased muscle mass, strength and physical function.

ACE-031 Clinical Development Program

Acceleron is developing ACE-031 to treat muscle-loss caused by:

* Muscular Dystrophy (MD)
* Amyotrophic Lateral Sclerosis (ALS)
* Cancer-Related Muscle Loss

By restoring skeletal muscle mass, strength and function, ACE-031 may offer hope to patients with these diseases. Acceleron expects to enter clinical trials with ACE-031 in early 2008.

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kashif mughal said...

ACE-031, the lead product in Acceleron’s muscle program, is being developed to treat diseases involving the loss of muscle mass.