Addex Therapeutics, a leading company pioneering allosteric modulation-based drug discovery and development, and the Dystonia Medical Research Foundation (DMRF) announced entering a collaboration to explore the use of dipraglurant to treat dystonia, the third most common movement disorder following essential tremour and Parkinson's disease.

Dipraglurant, a novel small molecule inhibitor of the metabotropic glutamate receptor 5, has shown promise in the treatment of levodopa-induced dyskinesia and dystonia in Parkinson's disease. Dipraglurant has also been shown to normalise the effects of the TOR1A/DYT1 dystonia mutation in the brains of mice. The objective of the collaboration is to design a detailed development plan and regulatory path as well as identifying key option leaders and patients for a phase 2 clinical trial. In addition, Addex recently reported on 9 January, plans to start clinical testing of the therapeutic effect of dipraglurant in patients with cervical dystonia in collaboration with Professor Dirk Dressler of The Hannover Medical School.

"The DMRF and Addex each embody spheres of expertise that complement the other very well," said DMRF president Art Kessler, who was diagnosed with dystonia as a child. "This drug represents an important opportunity for the dystonia community to examine a potential new treatment option in collaboration with established experts in drug discovery and development."

"The collaboration with the DMRF will give Addex access to unique networks of research and clinical experts in the field of dystonia" says, Sonia Poli, CSO at Addex. "Dipraglurant has shown robust efficacy in multiple models of dystonia and we look forward to collaborating with DMRF to evaluate dipraglurant in dystonia patients."

Dystonia is a neurological disorder characterised by persistent or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. The movements are usually patterned and twisting, and may resemble a tremour. Symptoms originate from an imbalance of neurotransmitters in the brain. There are multiple forms of dystonia, and up to 100 diseases and conditions include dystonia as a prominent symptom. Dystonia may affect a single body area or be generalised throughout multiple muscle groups. Dystonia affects men, women, and children of all ages and backgrounds. Estimates suggest that no fewer than 300,000 people are affected in the United States and Canada alone. Early onset primary dystonia are rare and frequently have a genetic basis (e.g. DYT1) and can progress to affect several parts of the body. Dystonia causes varying degrees of disability and pain, from mild to severe.

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), with potential to be used in combination with levodopa or dopamine agonists or as a standalone treatment for Parkinson's disease levodopa-induced dyskinesia (PD-LID), motor and non-motor symptoms of Parkinson's disease and other movement disorders. In a double-blind, placebo-controlled, US and European phase 2 study in PD-LID, data 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 reduced dystonia severity in addition to chorea, the two major LID components. 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. Additional endpoints include the Unified Parkinson's Disease Rating Scale (UPDRS), the Clinician & Patient Global Impression of Change (CGIC & PGIC), and an evaluation of the patients' mood using the Hospital Anxiety & Depression Score. The trial was supported by a grant from The Michael J. Fox Foundation for Parkinson's Research.

The Dystonia Medical Research Foundation (www.dystonia-foundation.org) is a 501c3 non-profit organisation dedicated to advancing research for improved dystonia treatments and ultimately a cure, promoting awareness, and supporting the well-being of affected individuals and families. Since 1976, the DMRF has supported and stimulated the dystonia research field. Work supported by the DMRF has led to an overall better understanding of dystonia as well as breakthroughs in genetics and therapeutics. The Foundation also provides patient education and support resources.