CAMBRIDGE, Mass.--(BUSINESS WIRE)--Scholar Rock, a biotechnology company focused on discovering and developing drugs that selectively target growth factors in the disease microenvironment, today announced the publication of “Tolloid cleavage activates latent GDF8 by priming the pro‐complex for dissociation” in The EMBO Journal in collaboration with the laboratories of Prof. Timothy Springer (Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Boston Children’s Hospital) and Prof. John R. Engen (Dept. of Chemistry and Chemical Biology, Northeastern University).
Myostatin (also known as GDF8) is a key signaling protein that contributes to the regulation of muscle mass and function. Initially produced by muscle in a latent inactive form, myostatin can be activated under certain conditions by sequential enzymatic steps. For the first time, the new study provides an understanding at the molecular level of the structural changes that take place in the protein during this activation process, and the central role of the tolloid enzyme in generating active myostatin. Insight into the activation mechanism of myostatin and other related proteins is central to the drug discovery platform established at Scholar Rock for the development of novel therapies for the treatment of many severe diseases.
“Deploying deep structural understanding of growth factors and their activation is opening a profound new way to intervene in human disease,” said Alan J. Buckler, Ph.D., Chief Scientific Officer of Scholar Rock. “SRK-015, our clinical candidate for the treatment of muscle atrophy and wasting disorders, exemplifies the strong potential of targeting specific structural states of myostatin with the objective of providing superior therapeutic outcomes.”
The proprietary therapeutic antibody, SRK-015, was discovered and designed by Scholar Rock to selectively and locally target the latent form of myostatin with the ability to specifically block its intramuscular activation. In a variety of preclinical models of muscle atrophy, SRK-015 has demonstrated improvement in muscle function. SRK-015 is initially being developed by Scholar Rock for the improvement of muscle strength and function in patients with Spinal Muscular Atrophy (SMA) with the treatment of additional neuromuscular diseases to follow.
About SRK-015
SRK-015 is a selective and local inhibitor of
the supracellular activation of latent myostatin. Myostatin, a member of
the TGF-beta superfamily of growth factors that is expressed primarily
in skeletal muscle cells, is a genetically validated target that
regulates muscle mass. Scholar Rock is actively working to advance
SRK-015 into clinical trials that will evaluate the potential to improve
muscle strength and motor function in patients with Spinal Muscular
Atrophy (SMA). Scholar Rock plans to develop SRK-015 both in SMA
patients who are on therapies aimed at upregulating the expression of
SMN and as monotherapy in certain subpopulations of SMA patients.
SRK-015 is an investigational drug candidate. The effectiveness and
safety of SRK-015 have not been established and SRK-015 has not been
approved by the FDA or any other regulatory agency.
About SMA
Spinal Muscular Atrophy (SMA) is a rare, and often
fatal, genetic disorder that affects approximately 1 in every 10,000
births. This disease is due to defects in the SMN1 gene that produces
SMN, a protein important for the survival and function of lower motor
neurons. Deterioration and loss of lower motor neurons that innervate
skeletal muscle lead to significant muscle atrophy, particularly in
fast-twitch fibers. Muscle weakness is the most common and prominent
feature of SMA, leaving many patients suffering from difficulty in
performing many basic motor functions. While there has been meaningful
progress in the development of therapeutics that address the underlying
SMA genetic defect, there continues to be a high unmet need for
therapeutics that directly address muscle atrophy. Directly targeting
the weakening of skeletal muscle may lead to improvements in muscle
strength and motor function that could positively impact patients with
SMA.
About Scholar Rock
Scholar Rock is discovering and
developing a pipeline of innovative new medicines to treat a range of
serious diseases in which growth factors play a fundamental role,
including neuromuscular diseases, cancer and fibrosis. By focusing on
newly elucidated biology of growth factor activation, Scholar Rock has
developed insights which allow us to selectively target growth factors
in the disease microenvironment – through the mechanism of modulating
supracellular activation. With our proprietary technology, we are
developing novel medicines aimed at achieving therapeutic effects
specifically at the source of disease to deliver new solutions for
patients. Scholar Rock is led by a highly-experienced management team of
leaders who have built successful biotechnology companies, and is backed
by leading investors.
