The Michael J Fox Foundation for Parkinson's Research has awarded $1,000,000 grant to Addex Therapeutics to help fund continued human clinical testing of dipraglurant for the treatment of Parkinson's disease levodopa-induced dyskinesia (PD-LID).
One-third of people with PD develop dyskinesia within four to six years of beginning levodopa treatment; this increases to approximately 90 per cent after nine or more years. Patients with Parkinson's disease (PD) can live 10-20 years after diagnosis; however, PD-LID is a leading cause of disability in this growing patient population.
"Dyskinesia is a top priority for our Foundation because of its significant negative impact on patients' quality of life," said Todd Sherer, Ph.D., chief executive officer of The Michael J Fox Foundation. "Candidates such as dipraglurant and other innovative therapies in development offer the possibility of improved quality of life through better symptomatic treatment of Parkinson's. Dipraglurant targets a molecular mechanism that our Foundation has been investing in since 2005 and we are pleased to take part in its continued progress to the clinic. We are enthusiastic about funding this work and hopeful that it may offer patients relief from a longstanding issue with the treatment of their disease."
Dyskinesias are the uncontrollable and disruptive movements that are caused by long-term use of levodopa (Sinemet), a dopamine replacement therapy and the gold-standard treatment for Parkinson's disease. There is no FDA-approved treatment for dyskinesia. Existing treatment options are limited and insufficient to address patients' medical needs. Patients are faced with a lose-lose situation: Take as much levodopa as needed to manage symptoms, and cope with dyskinesia; or take less medicine in an effort to delay or prevent dyskinesia, and cope with symptoms. The Michael J Fox Foundation has invested more than $26 million in dyskinesia-targeted research to date, including support for a successful phase II a trial of dipraglurant completed by Addex in 2012.
"We are extremely pleased to receive this grant from The Michael J Fox Foundation supporting the further development of dipraglurant," said Bharatt Chowrira, PhD., chief executive officer of Addex Therapeutics. "We believe the successful completion of the phase IIa study offers some promise that dipraglurant has the potential to significantly change both the way patients are treated as well as their quality of life. The work we will be able to pursue with this grant is critical to our continued advancement of this important approach to the treatment of PD-LID. Ultimately, we hope to see dipraglurant become the first drug to alleviate all PD-LID symptoms."
Dipraglurant is an oral, small molecule allosteric modulator that inhibits selectively the metabotropic glutamate receptor 5 (mGluR5), a Class C G-Protein Coupled Receptor (GPCR). Dipraglurant holds potential to be used in combination with levodopa or dopamine agonists, or as a standalone treatment for PD-LID, PD-related motor symptoms, dystonia, non-motor symptoms of PD and other movement disorders. Data from a phase IIa showed that dipraglurant met the primary objective of the study by exhibiting a good safety and tolerability profile. Dipraglurant also demonstrated a statistically significant reduction in LID severity with both 50 and 100 mg doses. Dipraglurant appears to reduce dystonia severity in addition to chorea, the two major LID components. In a double-blind, placebo-controlled study conducted in the US and Europe, the primary objective was to demonstrate safety and tolerability in PD-LID patients. In addition, the trial was designed to evaluate exploratory efficacy as a secondary objective. Efficacy was measured using the modified Abnormal Involuntary Movement Scale (mAIMS), patient diaries documenting "off-time" (impaired voluntary movement), "on-time" (with or without dyskinesia) and sleep. The trial was supported by a grant from The Michael J Fox Foundation for Parkinson's Research.
As the world's largest private funder of Parkinson's research, The Michael J Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers.
Addex Therapeutics is a development stage company focused on advancing innovative oral small molecules against rare diseases utilizing its pioneering allosteric modulation-based drug discovery platform.