Development of RAR ligands for the treatment of motor neuron disease

Amyotrophic lateral sclerosis (ALS) is a disorder with complex central causes and drugs directed to a single one of these may be less likely to be efficacious.  The retinoic acid receptors (RARs) are a family of receptors present in the CNS and which mediate the actions of vitamin A.  Ligands to the RARs have been shown in models of neurodegenerative disease to have both regenerative and anti-inflammatory properties.    The goal of this project is to test a series of novel agonists for these receptors, called RAR-Ms, in in-vitro assays for some of the cellular pathways disrupted in ALS, and take the most efficacious agonists into initial preclinical trials.  Our work to date has shown effectiveness of these agonists in assays for oxidative stress, glutamate excitotoxicity and that the agonists decrease the number of stress granules.