Addex ADX48621 Positive Primate Parkinson's Data

ADX48621 shows efficacy on both chorea and dystonia in PD-LID model

24-Nov-2009 - Switzerland

Addex Pharmaceuticals announced that in a non-human primate model of Parkinson's disease (PD) levodopa induced dyskinesia (LID), ADX48621 statistically and significantly inhibited LID. More specifically, the compound inhibited dose dependently both chorea and dystonia, the two major components of LID, without affecting the beneficial effects of levodopa. There is currently no approved treatment available for PD-LID. ADX48621 is a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator (NAM) that has completed Phase I testing and is scheduled to start Phase IIa testing in Parkinson's disease next year.

In the non-human primate MPTP model of PD-LID, the highest dose of ADX48621 (30mg/kg) abolished LID over the course of the experiment and a dose response was observed during the first two hours, reaching statistical significance for the highest dose tested. Importantly, statistically significant reductions were seen for both chorea and dystonia in a dose dependent fashion.

Addex reported earlier this year that when tested in a rat model, oral administration of ADX48621 dose-dependently reversed the catalepsy induced by haloperidol in three independent experiments. These data indicate that ADX48621 has potential as a treatment for Parkinsonian symptoms as well as LID symptoms.

Although other drug candidates have shown some efficacy on chorea, similar effects on dystonia have not previously been reported in this model with drug-like molecules either in development or on the market, (except with ADX10059, another mGluR5 NAM from Addex). ADX48621 is a next-stage mGluR5 NAM, which was generated from a separate chemical scaffold than ADX10059; both mGluR5 NAM have similar selectivity and activity at the target receptor. Addex' lead product ADX10059 is in Phase IIb development for gastroesophageal reflux disease (GERD) and migraine prevention. Addex plans to move ADX48621 forward in PD-LID, PD and dystonia.

https://www.bionity.com/en/news/109885/addex-adx48621-positive-primate-parkinson-s-data.html