Novel Agonists of mGluR5 receptor for the treatment of Multiple Sclerosis
Inventor (s): Cheryl F. Dreyfus, Jacques Roberge, Yangyang Huang
Date Awarded: October 2020
Summary:
In order to develop strategies to stimulate remyelination of Multiple Sclerosis (MS) lesions in the brain and spinal cord we have demonstrated that the metabotropic glutamate receptor 5 (mGluR5) agonist (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG) can reverse aspects of demyelination in two models (the cuprizone mouse model and the experimental autoimmune encephalomyelitis model of multiple sclerosis. The present study extends this work by developing assays that permit us to determine the active configuration of CHPG, and test 10-20 phenylglycine analogs that are commercially available. In the future compounds will be prepared to fill the holes in the series. The development of an mGluR5 agonist for MS has the potential to be an attractive drug development candidate. The neuroprotective effect of agonists and antagonists of mGluRs in CNS disorders such as ischemia, stroke, status epilepticus and various other neurodegenerative disorders is well-known and many companies have been active in developing mGluR5 antagonists/ agonists for these different indications. However, these molecules have never been shown to have efficacy in MS where there is a great medical need. We have shown activity with the agonist, R,S-2-chloro-5-hydroxphenylglycine (CHPG) of this mGluR5 receptor and believe we can develop patentable analogues of the active agent, CHPG.
