Addex reports positive pre-clinical efficacy data of ADX88178 in Parkinson’s disease study

The research conducted in collaboration with Merck showed that ADX88178 has the potential to improve the Parkinsonian symptoms as shown in two rodent models of dopamine depletion.

Addex chief scientific officer Graham Dixon said research shows that increasing mGluR4 activity could normalise the aberrant synaptic transmission resulting from dopamine depletion and restore normal activity in the brain circuits that control movement.

"The allosteric modulation approach enables modulation of mGluR4 with exquisite selectivity and our research provides compelling evidence and validation for mGluR4 activation for the treatment of Parkinson’s disease and a host of other indications through a non-dopaminergic approach," Dixon added.

ADX88178, a potent allosteric modulator of mGluR4 that shows selectivity against other metabotropic glutamate receptors, was found to enhance glutamate-mediated activation of human and rat mGluR4 with EC50 values of 3.5 and 9.1 nM respectively.

Oral administration of ADX88178 was associated with high bioavailability and was able to readily penetrate into the brain. ADX88178 was shown to reverse haloperidol-induced catalepsy in rats at 3 and 10mg/kg

The combination of ADX88178 with a low dose of L-DOPA allows dose-dependent reversal of the forelimb akinesia deficit induced to a bilateral 6-OHDA lesion of the striatum in rats.