ADX10059 can stop movement disorder dystonia symptoms caused by levadopa in Parkinson’s disease: Addex Pharma

ADX10059, an experimental drug can block movement disorder dystonia symptoms induced by levodopa in Parkinson’s disease patients, Addex Pharma said in a press statement.

ADX10059 study data in animal models of Parkinson’s disease levodopa induced dyskinesia (PD-LID) were presented at the Discovery on Target GPCR-based Drug Discovery conference in Boston.

ADX10059 had a statistically significant impact on dystonia, a neurological movement disorder seen in Parkinson’s disease and other conditions, including generalized dystonia, tardive dyskinesia, levodopa non responsive PD syndrome and multiple system atrophy,  Addex disclosed.

ADX10059 is the first-in-class negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5), a mechanism that is being tested in multiple indications.

ADX10059 is currently being evaluated in Phase IIb clinical trials for the treatment of gastroesophageal reflux disease (GERD) and to prevent migraine.

Separate announcements of data on ADX10059 from the two ongoing GERD trials are expected before year-end and early in 2010. The migraine study will report data early in the second quarter of 2010.

ADX10059 demonstrated significant efficacy in well-established preclinical models of PD and PD-LID. Importantly, these effects in PD and PD-LID were seen at doses and plasma concentrations that have shown efficacy in both clinical and preclinical studies with the compound in other indications.

ADX10059 effects on dystonia differentiate the Addex mGluR5 inhibitor within the PD indication but also present potential development opportunities for treatment of other types of dystonia.

When tested in the rat model, oral administration of ADX10059 dose-dependently reversed the catalepsy induced by haloperidol in three independent experiments.

mGluR5 inhibition reduces signaling activity of the neurotransmitter glutamate.

Currently marketed blockbuster drugs treat multiple indications by targeting other types of neurotransmitter signaling, including selective serotonin reuptake inhibitors (SSRIs) used to treat depression and dopamine receptor inhibitors used to treat schizophrenia.

What is dystonia?
Dystonia is a neurologic movement disorder characterized by sustained muscle contractions that frequently cause twisting or repetitive movements and abnormal, sometimes painful, postures or positions. Dystonia may affect any part of the body including the arms, legs, trunk, neck, head, or face.

PD-LID develops in most PD patients after receiving levodopa for several years. It is a complication caused by dopamine replacement therapy (i.e. levodopa). The two main components of LID are chorea and dystonia. Chorea is manifest as abnormal involuntary movements. Currently there are an estimated 1.2 million patients with PD-LID in the U.S.

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 U.S., where more than 1.5 million people currently have PD. While the condition usually develops after the age of 65, 15% of those diagnosed are under 50. PD affects both men and women in almost equal numbers.

Based in Geneva, Switzerland, Addex Pharmaceuticals discovers and develops allosteric modulators. Allosteric modulators are a different kind of orally available small molecule therapeutic agent, which we believe will offer a competitive advantage over classical drugs.

Addex Pharma has an agreement with Ortho-McNeil-Janssen Inc., a Johnson & Johnson company, on ADX71149, a positive allosteric modulator (PAM) of mGluR2, which is undergoing Phase I clinical testing and has potential for treatment of schizophrenia and anxiety.

Addex is also developing PAMs of mGluR4 and mGluR5 as drugs to treat Parkinson’s disease and schizophrenia, respectively under two separate agreements with Merck & Co., Inc.

GlaxoSmithKline and Roche have made equity investments in Addex.