Disarm Therapeutics Announces Science Publications Elucidating Structure and Function of SARM1
SARM1 structure enables drug design for diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and peripheral neuropathies
Description of the key role of the NADase pathway in cellular degeneration across species
Cambridge, Mass., Aug. 23, 2019 – Disarm Therapeutics, a biotechnology company creating a new class of disease-modifying therapeutics for patients with axonal degeneration, today announced the publication of two articles in Science that significantly advance the understanding of the structure and function of SARM1, a protein that is a critical regulator of cellular degeneration, and provide further support for the centrality of the NAD+-cleavage pathway in mediating cellular degeneration across multiple species. These new structural insights into SARM1 are expected to facilitate advances in drug design for diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and peripheral neuropathies.
In a paper focused on the structural basis of NAD+-cleavage activity, Dr. Bostjan Kobe of The University of Queensland, with Disarm scientists, has described the crystal structure of two important protein domains of SARM1, specifically the sterile alpha motif(SAM) and the toll/interleukin-1 receptor(TIR) domains. This advance makes possible the use of sophisticated computational tools to accelerate drug discovery via structure-based drug design, with far-reaching implications for drug development in neurodegenerative diseases.
“SARM1 is a potentially transformative drug target with broad therapeutic applications for patients, and Dr. Kobe’s research provides critical insights into the structure of SARM1 and the mechanism by which it mediates axonal degeneration,” said Alvin Shih, M.D., CEO of Disarm Therapeutics. “This work enables Disarm’s efforts to develop drugs for neurological diseases with substantial unmet medical need.”
In a concurrent paper also published today in Science, Disarm’s scientific co-founders, Dr. Jeff Milbrandt and Dr. Aaron DiAntonio, report the discovery thatthe TIR domain is a critical member of an evolutionarilyconserved family of NAD+-cleaving enzymes, and that this function is essential for innate immune signaling and the cell death response in plants.
“This important recent publication by Dr. Milbrandt and Dr. DiAntonio reinforces the critical NADase function of TIR domains in driving cellular degeneration across species,” said Rajesh Devraj, Ph.D., Chief Scientific Officer and co-founder of Disarm Therapeutics. “We look forward to continuing our partnership with Jeff and Aaron as we develop SARM1-targeted treatments for severe neurological diseases.”
Published in the Aug. 23, 2019 edition of Science, the papers are titled:
- NAD+cleavage activity by animal and plant TIR domains in cell death pathways
- TIR domains of plant immune receptors are NAD+-cleaving enzymes that promote cell death
About Disarm Therapeutics
Disarm Therapeutics is a biotechnology company that is creating a new class of disease-modifying therapeutics for patients with axonal degeneration, a central driver of neurological disease-causing disability and disease progression. By inhibiting the SARM1 protein, identified by the company’s scientific founders as the central driver of axonal degeneration, these therapeutics may prevent the loss of axons in chronic and acute diseases of the central, ocular, and peripheral nervous systems. For a broad range of diseases including multiple sclerosis, amyotrophic lateral sclerosis, glaucoma, and peripheral neuropathies, the therapeutic goal is to prevent further degeneration, stabilize disease, and allow for functional recovery. Disarm was founded by Atlas Venture, Dr. Jeffrey Milbrandt and Dr. Aaron DiAntonio of Washington University in St. Louis, and a team of exceptional scientists and drug developers committed to developing a new treatment paradigm for patients with neurological diseases. For more information, please visit www.disarmtx.com.
Sara Green, Ten Bridge Communications