SRK-015 is a laboratory-made monoclonal antibody against an inactive skeletal muscle protein called myostatin. The treatment was developed by Scholar Rock and is currently being investigated as a treatment for patients with spinal muscular atrophy (SMA) to improve muscle strength and motor function. 

How does SRK-015 work?

SRK-015 is a specific monoclonal antibody that selectively binds to the latent or inactive form of myostatin, a protein primarily found in skeletal muscle cells. Myostatin inhibits muscle growth by working in concert with other growth factors and hormones. The main role of myostatin is to help maintain healthy muscle mass.

In SMA, muscle tissue is weak and atrophied, so a plausible strategy to increase muscle mass is by inhibiting myostatin activity

When injected into the bloodstream, SRK-015 selectively binds to latent or inactive myostatin and prevents its conversion to an active form in muscle tissues. It does not affect the activity of other closely related factors such as GDF-11 or activin A, in contrast to traditional treatment approaches that block already activated (mature) myostatin or the myostatin receptor. In this way, SRK-015 is thought to have fewer side effects than other myostatin inhibitors.

SRK-015 in clinical trials

Research has shown that animals deficient in myostatin have increased muscle mass and strength. Myostatin inhibition with SRK-015 has shown similar results in preclinical studies.

A study in mice showed that SRK-015 helped improve muscle capacity and strength, and increased lean body mass, particularly in the fast-twitch muscle fibers affected in SMA.

Another study revealed that SRK-015 also effectively increased muscle mass and function in a mouse model of SMA and improved the bone structure of the animals. 

Scholar Rock announced in May 2018 that it had completed the first dose of treatment in a placebo-controlled, double-blind Phase 1 clinical trial testing SRK-015 in healthy volunteers. Positive final results, announced in June 2019, showed that SRK-015 was well-tolerated across all tested doses up to 30 mg/kg, with no dose-limiting toxicities reported.

Based on these findings, Scholar Rock started a Phase 2 trial called TOPAZ (NCT03921528) in May 2019 to test the treatment in patients with SMA type 2 and type 3. The trial aims to recruit 55 patients, 2 to 21 years old, at centers in the U.S., Italy, and Spain to evaluate the safety and efficacy of SRK-015.

Patients will be divided into three groups: groups 1 and 2 will be given 20 mg/kg of SRK-015 once every four weeks for one year. Group 3 will randomly receive an SRK-015 injection of 20 mg/kg or 2 mg/kg, once every four weeks for one year. The primary outcomes monitored will be safety and clinically meaningful outcomes in motor function or physical abilities based on the revised Hammersmith scale and the expanded Hammersmith functional motor scale.

Preliminary data from the trial released in November 2019 showed a dose-dependent increase of up to 100-fold in the levels of latent or inactive myostatin in the blood of patients. The analysis included 29 patients from the three groups: 12 patients from group 1, eight patients from group 2, and nine patients from group 3. These patients received a single dose of SRK-015 and were evaluated after four weeks. No safety issues were reported.

Scholar Rock plans to analyze interim safety and efficacy with a subset of patients at six months of treatment and expects the results in the first half of 2020. Topline results for the entire 12-month treatment period are expected in the fourth quarter of 2020 through the first quarter of 2021 when the trial is expected to be completed.

Other details

SRK-015 received orphan drug designation from the U.S. Food and Drug Administration in April 2018 and from the European Medicines Agency in December 2018.


Last updated: Nov. 26, 2019


SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.