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A New Approach to Treating Multiple Sclerosis

Press releases

September 19, 2017 – Disarm Therapeutics Unveils Breakthrough Approach to Treat Patients with Neurological Diseases by Preventing Axonal Degeneration
Announces $30 Million Series A Financing Led by Atlas Venture, with Co-Investors Lightstone Ventures and AbbVie Ventures


SARM1: the Central Driver of Axonal Degeneration

Small Molecule Inhibitors of SARM1 Prevent Chemotherapy-Induced Peripheral Neuropathy
Krauss R, Hughes R, Bosanac T, Devraj R, Engber T.
Presented at the 2020 Annual Meeting of the Peripheral Nerve Society. June 27, 2020

Axons Matter: The Promise of Treating Neurodegenerative Disorders by Targeting SARM1-Mediated Axonal Degeneration
Krauss R, Bosanac T, Devraj R, Engber T, Hughes R
Trends in Pharmacological Sciences (2020) 41: 281

cADPR is a gene dosage-sensitive biomarker of SARM1 activity in healthy, compromised, and degenerating axons
Sasaki S, Engber T, Hughes R, Figley M, Wu T, Bosanac T, Devraj R, Milbrandt J, Krauss R, DiAntonio A.
Experimental Neurology (2020) 329: e113252

Small Molecule Inhibitors of SARM1 Prevent Axonal Degeneration in vitro and in vivo
Krauss R, Bosanac T, Engber T, Devraj R, Hughes R
Presented at the 2019 Annual Meeting of the Society for Neuroscience. October 22, 2019

SARM1 Deletion Protects Axons in a Model of Inflammatory Demyelination
Krauss R, Hughes R, Bosanac T, Devraj R, Engber T
Presented at ECTRIMS 2019. September 13, 2019

NAD+ cleavage activity by animal and plant TIR domains in cell death pathways
Horsefield S, Burdett H, Zhang X, Manik MK, Shi Y, Chen J, Qi T, Gilley J, Lai J-S, Rank MX, Casey LW, Gu W, Ericsson DJ, Foley G, Hughes RO, Bosanac T, von Itzstein M, Rathjen JP, Nanson JD, Boden M, Dry IB, Williams SJ, Staskawicz BJ, Coleman MP, Ve T, Dodds PN, Kobe B
Science (2019) 365: 793

Vincristine and bortezomib use distinct upstream mechanisms to activate a common SARM1-dependent axon degeneration program
Geisler S, Doan R, Cheng G, Cetinkaya-Fisgin A, Huang S, Höke A, Milbrandt J, DiAntonio A
JCI Insight (2019) 4: e129920

SARM1 Loss of Function Prevents Degeneration of Peripheral and Central Axons
Krauss R, Hughes R, Bosanac T, Devraj R, Engber T
Presented at the Annual Meeting of the American Academy of Neurology. May 4, 2019

Axon degeneration: mechanistic insights lead to therapeutic opportunities for the prevention and treatment of peripheral neuropathy
DiAntonio A
Pain (2019) 160: S17

cADPR and NF-L are SARM1-Dependent Biomarkers of Axonal Structure and Function that Enable Therapeutic Discovery and Clinical Translation
Krauss R, Engber T, Hughes R, Bosanac T, Devraj R
Presented at the Molecular Mechanisms of Axon Degeneration Meeting. March 11, 2019

SARM1 Deletion Prevents Degeneration of Peripheral and Central Axons
Krauss R, Engber T, Devraj R, Bosanac T, Hughes R
Presented at the 2018 Annual Meeting of the Society for Neuroscience. November 3, 2018

Development of SARM1 Inhibitors to Treat Peripheral Neuropathies
Hughes R, Devraj R, Engber T, Bosanac T, Krauss R
Presented at the 2018 Peripheral Nerve Society Annual Meeting. July 23, 2018

Sarm1/Myd88-5 Regulates Neuronal Intrinsic Immune Response to Traumatic Axonal Injuries
Wang Q, Zhang S, Liu T, Wang H, Liu K, Wang Q, Zeng W
Cell Rep. (2018) 23: 716

Sarm1 Deletion, but Not WldS, Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy
Gilley J, Ribchester R, Coleman M
Cell Rep. (2017) 21:10

Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy
Turkiew E, Falconer D, Reed N, Höke A
J Peripher Nerv Sys. (2017) 22: 162

The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD+ Cleavage Activity that Promotes Pathological Axonal Degeneration
Essuman K, Summers DW, Sasaki Y, Mao X, DiAntonio A, Milbrandt J
Neuron (2017) 93: 1334

Prevention of vincristine-induced peripheral neuropathy by genetic deletion of SARM1 in mice
Geisler S, Doan RA, Strickland A, Huang X, Milbrandt J, DiAntonio A
Brain (2016) 139: 3092

SARM1-specific motifs in the TIR domain enable NAD+ loss and regulate injury-induced SARM1 activation
Summers DW, Gibson DA, DiAntonio A, Milbrandt J
Proc Natl Acad Sci (2016) 113: e6271

Axon Self-Destruction: New Links among SARM1, MAPKs, and NAD+ Metabolism
Gerdts J, Summers DW, Milbrandt J, DiAntonio A
Neuron (2016) 89: 449

SARM1 activation triggers axon degeneration locally via NAD⁺ destruction
Gerdts J, Brace EJ, Sasaki Y, DiAntonio A, Milbrandt J
Science (2015) 348: 453

Mitochondrial dysfunction induces Sarm1-dependent cell death in sensory neurons
Summers DW, DiAntonio A, Milbrandt J
J Neurosci (2014) 34: 9338

Sarm1-mediated axon degeneration requires both SAM and TIR interactions
Gerdts J, Summers DW, Sasaki Y, DiAntonio A, Milbrandt J
J Neurosci (2013) 22: 13569

Measuring Axonal Degeneration

Neurofilaments as biomarkers in neurological disorders
Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer M, Barro C, Kappos L, Comabella M, Fazekas F, Petzold A, Blennow K, Zetterberg H, Kuhle J
Nature Reviews Neurology (2018) 14: 577

Neurofilament light chain as disease biomarker in a rodent model of chemotherapy induced peripheral neuropathy
Meregalli C, Fumagalli G, Alberti P, Canta A, Carozzi VI, Chiorazzi A, Monza L, Pozzi E, Sandelius Å, Blennow K, Zetterberg H, Marmiroli P, Cavaletti G
Experimental Neurology (2018) 307: 129

Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis
Barro C, Benkert P, Disanto G, Tsagkas C, Amann M, Naegelin Y, Leppert D, Gobbi C, Granziera C, Yaldizli Ö, Michalak Z, Wuerfel J, Kappos L, Parmar K, Kuhle J
Brain (2018) 141: 2382

Serum Neurofilament Light: A Biomarker of Neuronal Damage in Multiple Sclerosis
Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A, Zecca C, Blennow K, Zetterberg H Leppert D, Kappos L, Gobbi, C, Kuhle J, and the Swiss Multiple Sclerosis Cohort Study Group
ANN NEUROL (2017) 81: 857

Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis
Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, Giovannoni G, Fratta P, Sidle K, Fish M, Orrell R, Howard R, Talbot K, Greensmith L, Kuhle J, Turner MR, Malaspina A
Neurology (2015) 84: 2247