Addex Therapeutics Ltd. announced positive preclinical data for its mGlu5 negative allosteric modulator (NAM) oral small molecule, dipraglurant, in a validated rodent model of dystonia, a spectrum of disorders, that includes several rare diseases and is characterized by debilitating involuntary muscle contractions and body movements. This is an area of high unmet medical need where many patients are left inadequately treated with the current standard of care. Dipraglurant demonstrated a robust and dose-dependent reduction in severity of a dystonia-like attack, induced by caffeine in the tottering mouse model.

These data are consistent with earlier reported Addex findings in a Phase 2a clinical trial measuring levodopa-induced dyskinesia in Parkinson's patients as well as a non-human primate model of Parkinson's-related dystonia. The validation of the tottering mouse model in the laboratory of Professor Hess has been funded in part by the Bachmann-Strauss Dystonia and Parkinson Foundation. The model recapitulates key genetic and phenotypic features of so called episodic neurological disorders, that involve aberrant calcium channel functioning and susceptibility to neurological attacks in response to stress, alcohol or caffeine.

In the study, acute, oral administration of dipraglurant (10, 30, 50 mg/kg) resulted in dose-dependent reductions of dystonia scores, achieving significant reductions at the highest dose in comparison to vehicle treatment. In a sub-group of experimental animals, dipraglurant fully blocked the onset of dystonia. These results demonstrate the potential of mGlu5 inhibition as a novel approach for the treatment of multiple types of dystonias, as well as other rare neurological conditions including familial hemiplegic migraine type 1, episodic ataxia type 2, and periodic paralysis.