Scholar Rock, a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, today announced the publication, “Specific Inhibition of Myostatin Activation is Beneficial in Mouse Models of SMA Therapy” in the peer-reviewed journal Human Molecular Genetics. The publication details preclinical studies demonstrating that a highly specific inhibitor of myostatin, SRK-015, a protein which inhibits muscle growth, effectively increased muscle mass and function in mouse models of SMA. In addition, despite baseline serum levels of inactive latent myostatin being lower in the SMA mice than in mice without disease, successful target engagement was observed as evidenced by increased levels of latent myostatin in serum following treatment. Together, the results support the potential for myostatin blockade as a therapeutic strategy to address motor functional deficits in SMA.
The preclinical results published today in Human Molecular Genetics demonstrated that specific blockade of myostatin activation, in conjunction with SMN upregulation treatment, improved muscle mass and function in a mouse model of SMA.
Highlights from the study include:
In a mouse model with a relatively more severe SMA phenotype, mice received four weeks of treatment with SRK-015 as well as optimal doses of the SMN upregulator that mimic the use of therapy to more fully restore SMN expression. This led to a significant increase in muscle strength, as demonstrated by a 44%-51% increase in maximal torque of the plantarflexor muscle group, compared to control animals treated only with optimal doses of the SMN upregulator over the same treatment period.
In a mouse model with a relatively less severe SMA phenotype, mice received four weeks of treatment with SRK-015, together with background therapy with optimal dosing of the SMN upregulator that was started shortly after birth. This resulted in a 20%-30% increase in maximal torque of the plantarflexor muscle group, compared to control animals not treated with SRK-015.
Treatment of SMA model mice with SRK-015 resulted in a multi-fold increase in serum levels of latent myostatin, which confirms the presence of the SRK-015 target in these models and successful target engagement from systemic administration of the drug.
SRK-015 works by inhibiting myostatin. Myostatin is a protein that works with other proteins and hormones to help regulate muscle mass. In healthy individuals, myostatin limits muscle growth and differentiation, to prevent muscles from growing too large. For individuals affected by SMA, inhibiting this protein may combat the muscle weakness and atrophy that characterizes the disease. A Phase 1 clinical trial in healthy volunteers is ongoing. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for SRK-015 for the treatment of SMA.
About Scholar Rock
Scholar Rock is a clinical-stage biopharmaceutical company focused on the discovery and development of innovative medicines for the treatment of serious diseases in which signaling by protein growth factors plays a fundamental role. Scholar Rock is creating a pipeline of novel product candidates with the potential to transform the lives of patients suffering from a wide range of serious diseases, including neuromuscular disorders, cancer, fibrosis and anemia.