The biotech company’s therapy targets the precursor to the growth factor myostatin, whose over-activation is linked to muscle atrophy. The study’s findings support SRK-015’s potential as a treatment for muscle wasting disorders, the researchers said.
Scholar Rock is working on moving the therapy into clinical trials of patients with spinal muscular atrophy, or SMA.
The study, “Blocking extracellular activation of myostatin as a strategy for treating muscle wasting,” was published in the journal Scientific Reports.
“Because of the well-established impact of myostatin signaling on muscle mass, a number of agents that target the myostatin signaling pathway have entered” clinical trials as potential treatments for muscle wasting, the researchers wrote.
These therapies have targeted the mature form of myostatin or its receptor on muscle cells, however — and they have had limited success.
Scholar Rock researchers decided to try blocking the activation of a myostatin precursor molecule called proMyostatin.
They learned that the most potent antibody they developed against myostatin, which they dubbed SRK-015, inhibited the activation of both myostatin and proMyostatin. Their work also led to them finding that proMyostatin is located mainly outside cells — in the space between muscle fibers.
“Our finding that most proMyostatin resides extracellularly in its primary target tissue, muscle, suggests that extracellular activation is a critical step in myostatin signaling,” they wrote.
Most importantly, they discovered that SRK-015 bound well with myostatin’s precursor, blocking its activation.
The result, they said, was preventing additional wasting in a mouse model of muscle atrophy, and increased muscle mass and function in healthy mice.
Overall, “we show that blocking the extracellular activation of growth factors is a potent method for preventing signaling, serving as proof of concept for a novel therapeutic strategy,” they wrote.
“The results of this study demonstrate the power of focusing therapeutic intervention in growth factor signaling one step upstream of the signaling event,” Alan J. Buckler, the chief scientific officer of Scholar Rock, said in a press release.
“By understanding the processing and release of growth factors in the tissue microenvironment, we see a vast opportunity to improve therapeutic outcomes in many severe diseases with serious unmet medical needs,” he said. “We are particularly excited to further our understanding of myostatin’s role as we begin clinical trials of SRK-015 in the coming months.”