Several GPCRs have been implied in the pathology of Alzheimer’s disease among them mGlu2. In a collaboration with Prof.S.Gandy (Mount Sinai, New York) the role of mGlu2 is being explored.
Exposure of synaptoneurosomes with a group II agonist leads to a rapid increase in Abeta 42 peptides, which is blocked by BCI-632. In addition, chronic dosing with BCI-838 in two models of amyloid deposition lead to small but significant decreases in various amyloid peptides and small but significant improvements in cognitive impairment. Moreover, BCI-632 enhances social recognition. Other companies are pursuing mGlu2 negative allosteric inhibitors for cognition and found those to be active in reversing scopolamine induced disruptions in DMTP test in rodents and non-human primates. All these data together suggest, that antagonism to these receptors could be useful as symptomatic as well as potential disease modifying therapy for AD.