Addex Pharmaceuticals Awarded Michael J. Fox Foundation Grant for ADX48621 to Treat Levodopa-Induced Dyskinesia in Parkinson's Disease
Published: Sep 08, 2010
"People with Parkinson's report that the side-effects of levodopa treatment are one of the most difficult aspects of living with the disease. We believe ADX48621 has the potential to improve the quality of life for patients suffering from the undesirable effects of long-term dopamine replacement," said Katie Hood, CEO, The Michael J. Fox Foundation. "ADX48621 targets a molecular mechanism that our Foundation has been investing in since 2005. We're enthusiastic about funding this clinical work and the hope that it may bring to patients."
ADX48621 is a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator (NAM). It already has successfully completed Phase I testing in three studies involving a total of 130 patients, including older healthy volunteers. A Phase II study of ADX48621 to treat PD-LID is expected to start in the U.S. and EU during the fourth quarter of 2010.
"We are honored to receive this grant from The Michael J. Fox Foundation supporting ADX48621 development," said Vincent Mutel, CEO of Addex. "The reduction in both major components of LID, which we observed after administering ADX48621 to non-human primates with LID, has not been reported with other drugs on the market or in development. As a result, we believe that it could become the first drug capable of alleviating all LID symptoms."
Levodopa and dopamine agonists are effective treatments for the signs and symptoms of Parkinson's disease; but long-term levodopa use results in the emergence of side effects, especially abnormal involuntary movement, termed levodopa-induced dyskinesia or LID. Statistics show that half of patients develop LID during the first five years of treatment. The two main components of LID are chorea and dystonia. Chorea is manifest as sudden rapid uncontrolled movements. Dystonia is manifest as slow writhing type movements and sustained muscle contractions, which can be painful.
In addition to reducing chorea, the stereotypical trembling often associated with PD patients, ADX48621 is the first drug-candidate to effectively reduce dystonia in the non-human primate "MPTP model" of PD-LID.
mGluR5 inhibition reduces signaling activity of the neurotransmitter glutamate. The loss of dopamine producing cells observed as a result of Parkinson's disease leads to excess of glutamatergic stimulation in the brain's striatopallidal pathway. The mGluR5 are found abundantly in the striatum. Because most drugs for PD work via the dopaminergic system, inhibition of mGluR5 could provide a novel and complementary treatment option for PD and PD-LID. Indeed, published research shows that ADX48621 and other mGluR5 inhibitors have reduced LID and generated anti-Parkinsonian effects in animal models of PD-LID and Parkinson's disease, respectively. In addition, one small clinical study already has shown that mGluR5 inhibition reduced LID symptoms in humans with PD-LID.
The Michael J. Fox Foundation was founded in 2000. The Michael J. Fox Foundation for Parkinson's Research is dedicated to ensuring the development of a cure for Parkinson's disease through an aggressively funded research agenda. The Foundation has funded almost $200 million in research to date.
Addex Pharmaceuticals (www.addexpharma.com) discovers and develops allosteric modulators for human health and is focused on validated therapeutic targets for diseases of the central nervous system, metabolic disorders and inflammation. Subject to regulatory approvals, Phase II clinical trials are expected to start soon in four indications for two lead products: ADX48621, an mGluR5 negative allosteric modulator (NAM), in dystonia and Parkinson's disease levodopa-induced dyskinesia (PD-LID); and ADX71149, an mGluR2 positive allosteric modulator (PAM), in schizophrenia and anxiety. A third product, ADX71943, GABA-B receptor PAM with potential for chronic pain, is scheduled to enter Phase I testing in 2011. In addition, Merck & Co., Inc. has licensed rights to two preclinical products: mGluR4 PAM for Parkinson's disease and mGluR5 PAM for schizophrenia. Additional preclinical discovery stage programs include: mGluR2 NAM; GLP1R PAM; IL1R1 NAM; and TNFR1 NAM. Roche Venture Fund and SR-One, corporate venture arm of GlaxoSmithKline, are investors in Addex.