OREANDA-NEWS. Addex Therapeutics, announced today the successful completion of the first part of a project funded by the Swiss Commission for Technology and Innovation (CTI) to characterize Addex' mGlu4 and mGlu7 receptor allosteric modulators in models of neurodegenerative and psychiatric diseases. The program was conducted in collaboration with the Center for Psychiatric Neuroscience (CNP) at the Centre Hospitalier Universitaire Vaudois (CHUV), and the Laboratory for the Study of Neurodegenerative Diseases (LEN) at Ecole Polytechnique F?d?rale de Lausanne (EPFL).

ADX88178, an mGluR4 positive allosteric modulator (PAM), was tested in a preclinical model of Parkinson's disease where rats were unilaterally injected in the substantia nigra with an adeno-associated viral vector encoding human alpha-synuclein which induces motor impairments, dopamine loss and important features of the idiopathic disease, including alpha-synuclein accumulation and degeneration of nigral dopaminergic neurons. ADX88178 administered chronically (60 mg/kg subcutaneously for 10 weeks) was able to induce a reduction in the motor impairments observed in the model, but without significantly affecting the progression of the observed neurodegeneration.

The effect of ADX71743, an mGluR7 negative allosteric modulator (NAM) and ADX88178 were tested on electrophysiological slice recordings at the thalamus-to-amygdala synapses. The experiments demonstrated that ADX71743 and ADX88178 were able to impact the excitatory neurotransmission in the amygdala. This is an important discovery as emotional stimuli get relayed through auditory thalamus into amygdala which is an important pathway involved in the establishment of fear. These findings provide a mechanistic explanation of the anxiolytic effects previously observed in preclinical models of anxiety with these compounds (Kalinichev et al. 2013). A peer reviewed publication synthetizing all data obtained in these studies is in preparation.

Following the successful completion of the planned studies, the team has recently been awarded a second grant by CTI of CHF660'240 to support the continued characterization of mGluR4 and mGluR7 compounds in fear conditioning and reward models using combined electrophysiological and optogenetic methods.

"The results of these studies demonstrate the potential effect our unique molecules may have on the processes underlying Parkinson's disease and on extinction of learned fear, a central process believed to be affected in Post-Traumatic Stress Syndrome.", commented Dr Robert L?tjens, Head of Discovery at Addex. "With the continued support of CTI and our collaboration partners at CHUV and EPFL, we are now building on these data to further advance our understanding of the important roles played by mGlu4 and mGlu7 receptors in neurological and psychiatric disorders."