Merck Sharp & Dohme LLC has identified receptor-interacting serine/threonine-protein kinase 1 (RIPK1; RIP-1) inhibitors reported to be useful for the treatment of amyotrophic lateral sclerosis and inflammatory disorders.
University of Oxford scientists have presented data from deep proteomics of cerebrospinal fluid (CSF) in search of proteins with diagnostic or prognostic value in amyotrophic lateral sclerosis (ALS). Analysis was performed using CSF samples from 40 ALS patients, 15 controls (healthy individuals) and 8 mimicking conditions.
Researchers from Autifony Therapeutics Ltd. presented preclinical data for the novel potent Kv3 channel positive modulator, AUT-00201, which is currently being evaluated in early clinical studies for the treatment of patients with progressive myoclonus epilepsy type 7 (EPM7).
Microtubule acetylation and impaired axonal transport have been proposed as mechanisms causing amyotrophic lateral sclerosis (ALS). Furthermore, histone deacetylase 6 (HDAC6) is known to play a role in acetylation of α-tubulin, a subunit of microtubules. ACY-738 is an HDAC6 inhibitor that has been reported to slow neuron degeneration in Alzheimer’s disease and ALS models by increasing acetylation of α-tubulin.
Psychiatric indications, such as depression, schizophrenia and bipolar disorder, share a common feature of elevated expression of pro-inflammatory markers in the periphery and/or central nervous system. Based on this, it is believed that combined immuno- and neuromodulatory activities of phosphodiesterase 4 (PDE4) inhibitors may represent a promising new therapeutic strategy for various psychiatric indications.
Subcommisural organ (SCO)-spondin is a brain-specific glycoprotein essential for neurogenesis with a high impact on neuronal development; thus, reduction in the production of SCO-spondin may lead to a lack of regeneration in neurological disorders.
Previous research has demonstrated that systemic administration of a P2X7 agonist improved motor performance in a mouse model of amyotrophic lateral sclerosis (ALS) through enhancing satellite cells and the muscle pro-regenerative activity of infiltrating macrophages.
Researchers from Anhui University presented the discovery and preclinical evaluation of novel negative allosteric modulators (NAMs) of the metabotropic glutamate mGlu5 receptor.
Researchers from Delix Therapeutics Inc. recently presented preclinical pharmacology data for DLX-001, a novel orally bioavailable, nonhallucinogenic neuroplastogen being developed for the treatment of neuropsychiatric diseases.
Axonal degeneration is a key early pathogenic driver of amyotrophic lateral sclerosis and other neurodegenerative diseases. Activation of calpain-2 (CAPN2) is thought to be the critical effector behind axonal degeneration. Amylyx Pharmaceuticals Inc. has presented data on their CAPN2 inhibitor antisense oligonucleotide (ASO) AMX-0114 as a potential therapeutic for axonal degeneration.