NT-1654 / Neurotune - LARVOL DELTA

Modulation of the Acetylcholine Receptor Clustering Pathway Improves Neuromuscular Junction Structure and Muscle Strength in a Mouse Model of Congenital Myasthenic Syndrome. (PubMed, Front Mol Neurosci) - "In this study, we aimed to determine if a compound (NT1654), developed to stimulate the acetylcholine receptor (AChR) clustering pathway, would benefit a mouse model of CMS caused by a loss-of-function mutation in Agrn (Agrn mouse)...We hypothesize this occurs through the AChR clustering pathway in Agrn mice. Future studies should investigate if this may represent a viable treatment option for patients with CMS, especially those with mutations in proteins of the AChR clustering pathway."

Journal • Preclinical • CNS Disorders • Myasthenia Gravis

Increasing Agrin Function Antagonizes Muscle Atrophy and Motor Impairment in Spinal Muscular Atrophy. (PubMed, Front Cell Neurosci) - "Studies of NMJ morphology on whole-mount diaphragm preparations revealed that NT-1654-treated SMA mice had more mature NMJs and reduced NF accumulation, compared to vehicle-treated SMA mice. We conclude that increasing agrin function in SMA has beneficial outcomes on muscle fibers and NMJs as the agrin biological NT-1654 restores the crosstalk between muscle and MNs, delaying muscular atrophy, improving motor performance and extending survival."

Journal • Biosimilar • Gene Therapies

Modulation of Agrin and RhoA Pathways Ameliorates Movement Defects and Synapse Morphology in MYO9A-Depleted Zebrafish. (PubMed, Cells) - "In addition, treatment of zebrafish with fasudil, a ROCK inhibitor, also provided improvements to the morphology of NMJs in early development, as well as rescuing movement defects, but not to the same extent as NT1654 and not at later time points. Therefore, this study highlights a role for MYO9A at the NMJ, the first unconventional myosin motor protein associated with a neuromuscular disease, and provides a potential mechanism of action of MYO9A-pathophysiology."

Journal

Targeting the neuromuscular junction to treat congenital myasthenic syndromes and inherited motor neuropathies (AAN 2020) - "Our data show that NT1654 is safe and improves neuromuscular transmission in these mice models, as measured by morphological analysis of the NMJ, biochemical and functional analysis of the muscle."