Dipraglurant in PD-LID

Dipraglurant is a novel oral small molecule, which inhibits the metabotropic glutamate receptor 5 (mGluR5), and has potential to be used in combination with levodopa or dopamine agonists for the treatment of Parkinson’s disease (PD).

Our initial focus is on testing dipraglurant for the treatment of PD levodopa-induced dyskinesia (PD-LID). Together with a partner, we hope to study dipraglurant’s potential for treatment of the non-motor symptoms of PD (e.g. anxiety, depression and impulse control disorders), motor symptoms of PD and also non-parkinsonian dystonias.

During the neurodegenerative process of PD, loss of striatal dopaminergic neurons results in an increase in gluatamatergic output from the substantia nigra. There is an abundance of mGluR5 located in the striatum and has been implicated in the excess glutamate activity observed in PD. Blockade of mGluR5 has been shown to have anti-PD and antidyskinetic effects in a variety of animal models as well as early trials in patients.

We believe a successful treatment for PD-LID will change the way Parkinson’s disease is treated, by enabling physicians to use the most effective drug for Parkinson’s disease – levodopa – earlier and more aggressively. In addition, based on robust preclinical data, potential label expansions for dipraglurant include: PD motor symptoms and/or non-motor symptoms, like co-morbid anxiety and depression, as well as non-parkinsonian dystonias.

We recently launched a receptor occupancy study, following a successful Phase IIa trial, under the direction of Dean F. Wong, MD, PhD, of the Department of Radiology, Psychiatry and Neuroscience at John Hopkins University. The study aims to assess brain mGluR5 occupancy using positron emission tomography (PET) following dosing of dipraglurant in healthy subjects and to assess the relationship between dipraglurant plasma concentration and brain mGluR5 occupancy. The Michael J. Fox Foundation for Parkinson’s Research provided funding for the trial.  

No drug is approved for PD-LID and LID has been identified by the regulatory authorities, patient advocacy groups such as Michael J. Fox Foundation and key opinion leaders as a very important unmet medical need. The potential market opportunity for dipraglurant in Parkinson’s disease is well in excess of $1 billion, according to market research carried out by Datamonitor for Addex. Further label expansion outside of Parkinson’s disease, for example to treat non-parkinsonian dystonias, could more than double the peak sales potential for dipraglurant.