Allosteric modulation company Addex Pharmaceuticals announced the extension of its research collaboration with Merck & Co, Inc, through an affiliate, for an additional year. The collaboration is focused on developing positive allosteric modulators (PAM) of the metabotropic glutamate receptor 4 (mGluR4) for the treatment of Parkinson's disease and other undisclosed indications.

Addex will receive research funding from Merck in addition to the original financial terms, which include milestones and royalties.

Earlier this year Addex disclosed that a preclinical study had shown that the collaboration had yielded orally available mGluR4 PAM with efficacy in an animal model of Parkinson's disease.

"We are delighted that Merck values the contribution of our allosteric modulator discovery platform and wishes to include us in building further upon the excellent progress this programme has made to date," said Emmanuel Le Poul, head of the CNS Business Unit at Addex.

"Developing innovative non-dopaminergic drugs for Parkinson's disease is an increasingly important part of our work at Addex," said Vincent Mutel, CEO of Addex. "We are proud to be advancing mGluR4 PAMs with our collaborators at Merck."

Under the terms of the exclusive collaboration and license agreement, first announced in December 2007, Addex received US$ 3 million upfront and has received two preclinical milestones of US$ 250,000 and US$ 500,000, to date. Addex is eligible to receive up to US$ 106.5 million in research, development and regulatory milestones for the first product developed for multiple indications. Additional milestones of up to US$ 61 million would be payable if a second and third product is developed. Addex is eligible to receive undisclosed royalties on sales of any products resulting from this collaboration. Merck is responsible for clinical development. Extension of the research collaboration allows Addex to recognize US$ 1.8 million in research funding over 12 months beginning on December 1, 2009.

Glutamate, like dopamine and serotonin, is a key neurotransmitter in the human brain, an important signalling molecule involved in control of multiple brain functions ranging from motor control to mood. In Parkinson's disease, the death of dopamine producing neurons leads to excess glutamate signalling.

Parkinson's disease is a degenerative disease of the brain that often impairs motor skills, speech, and other functions. It is estimated that 60,000 new cases are diagnosed each year in the US, where more than 1.5 million people currently have PD. While the condition usually develops after the age of 65, 15 per cent of those diagnosed are under 50. PD affects both men and women in almost equal numbers.

mGluR4 may play an important role in Parkinson's disease. Current treatments focus on dopamine-replacement strategies, however most patients reach a stage where dopaminergic treatments are no longer effective. There can also be debilitating side effects with dopaminergic treatments, especially levodopa induced dyskinesia, and many patients are encouraged to limit doses so their side effects will appear later and be less cumbersome. The recent success of surgical approaches suggests that bypassing the dopamine system may provide a more effective treatment strategy. It is believed that selective activation of mGluR4 is one way to do this and could correct the circuitry that modulates motor excitability via a non-dopaminergic mechanism.

Addex Pharmaceuticals discovers and develops allosteric modulators for human health.