Addex Awarded Michael J. Fox Foundation Grant for ADX48621 to treat Levodopa-Induced Dyskinesia in Parkinson's

10-Sep-2010 - Switzerland

Addex Pharmaceuticals Ltd announced that it has been awarded a $900,000 grant from the Michael J. Fox Foundation (MJFF) to help fund a Phase II study of ADX48621 for the treatment of Parkinson’s disease levodopa-induced dyskinesia (PD-LID). Patients with PD can live 10-20 years after diagnosis; however, LID is a leading cause of disability in this growing patient population.

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.

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.

https://www.bionity.com/en/news/122660/addex-awarded-michael-j-fox-foundation-grant-for-adx48621-to-treat-levodopa-induced-dyskinesia-in-parkinson-s.html