SRK-015 is an investigational antibody being developed by Scholar Rock, a biotech company, to improve muscle strength and motor function in patients with spinal muscular atrophy (SMA). This neurodegenerative disease is caused by defects in the SMN1 gene that leads to a loss of motor neurons and, subsequently, to muscle atrophy (weakness).

SRK-015 has shown promising results in preclinical studies, and the company is planning to advance the treatment into clinical trials in SMA patients.

How SRK-015 works

SRK-015 is a selective and local inhibitor of the latent (not completely active) form of myostatin, a protein expressed primarily in skeletal muscle cells that largely works to inhibit muscle growth. In concert with other growth factors and hormones, myostatin helps to maintain a healthy muscle mass.

By selectively inhibiting latent myostatin from becoming active in muscle, SRK-015 does not affect the activity of other closely related factors (such as GDF-11 or activin A) as happens in traditional treatment approaches that block already activated (mature) myostatin or the myostatin receptor, potentially resulting in side effects.

Preclinical studies

Animals deficient in myostatin have been shown to have increased muscle mass and strength. SRK-015-mediated myostatin inhibition has shown similar results in preclinical studies that were presented at the 2017 Cure SMA Annual Conference.

Studies in primates and mice showed that SRK-015 helps to improve muscle capacity and strength. It increased primates’ lean body mass, particularly in fast-twitch muscle fibers, a type of muscle fiber that is affected in SMA.

In a mouse model of SMA, a combination of SRK-015 and a therapy that corrects the underlying genetic defect in SMA (corrector therapy) significantly improved calf muscle strength in the mice, compared to the corrector therapy alone.

Another preclinical study, conducted by the Miami Project to Cure Paralysis (MPCP) in collaboration with Scholar Rock, demonstrated beneficial effects of SRK-015 in a model of spinal cord injury (SCI). Study results, presented at the 35th Annual National Neurotrauma Symposium, revealed that SRK-015 decreased muscle atrophy, reduced fat infiltration into muscles, and improved muscle pathology and function. These results demonstrate the potential of SRK-015 in a wide range of neuromuscular disorders.

The future

This preclinical data, including the specific activity against myostatin and selective effects on fast-twitch muscle fibers, are important when considering chronic therapy in children.

Scholar Rock is working to advance SRK-015 into clinical trials, expected to begin in mid- 2018. The company plans to develop SRK-015 in clinical trials both as a monotherapy in patients with certain types of SMA, and as a treatment used in combination with corrector therapies addressing the underlying genetic defect in SMA.

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