Addex Dipraglurant Reduces Motor Abnormalities in a Preclinical Model Relevant for Several Rare Types of Dystonia

Addex Therapeutics, a leading company pioneering allosteric modulation-based drug discovery and development, 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 include several rare diseases. 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 effects of dipraglurant in the mouse model are very compelling. They provide additional support for further exploration of mGlu5 inhibitors as a novel treatment for dystonia and also open new therapeutic avenues" said Professor Ellen Hess at Emory University (USA) in whose laboratory the study was performed.

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.

"We are pleased that we continue to see broad therapeutic application for dipraglurant," said Bharatt Chowrira, CEO at Addex. "As we continue to seek a partner to advance dipraglurant in Parkinson's levodopa-induced-dyskinesia, we see great opportunity to take the compound forward in several rare disease indications including certain forms of dystonias. We look forward to starting Phase 2 clinical testing in the second half of 2013 with this potentially important movement disorder therapeutic".