Phase 2 Trial of Dapansutrile for Early Parkinson's Disease

A recent initiative has been launched to explore the potential of a drug called dapansutrile in managing early-stage Parkinson's disease. The study, backed by a grant from Cure Parkinson’s under its International Linked Clinical Trials (iLCT) program, will be a Phase 2 clinical trial conducted at the University of Cambridge in the UK. Dr. Caroline H. Williams-Gray, a leading figure in Parkinson’s research, will be at the helm of this trial, which is set to be supported by the Neuroscience Theme of the Cambridge Clinical Trials Unit and the NIHR Cambridge Biomedical Research Centre.

Dapansutrile, an NLRP3 inhibitor, is a novel therapeutic agent that aims to mitigate the inflammatory response associated with Parkinson's disease. This approach is significant as it could potentially alter the disease's progression. The clinical trial will involve treating patients for a duration of up to 12 months, which will allow researchers to assess the drug's impact on both motor function and non-motor symptoms.

Parkinson's disease is recognized as the fastest-growing neurological condition globally. The disease's movement-related symptoms typically emerge after a substantial loss of dopamine-producing cells in a brain region known as the substantia nigra. Importantly, previous research has shown that dapansutrile can protect these substantia nigra cells in mouse models.

The study, titled "Anti-inflammatory Intervention with Dapansutrile (OLT1177®) for Parkinson’s Disease Modification (DAPA-PD): A Randomised Double-Blind Placebo-Controlled Phase II Trial," is planned to begin in mid-2024, pending the completion of contractual agreements and regulatory approvals. The trial will involve 36 participants suffering from early-stage Parkinson's disease and will consist of a six-month treatment period with a placebo control, followed by an optional six-month open-label phase.

Dr. Williams-Gray has expressed the urgent need for a targeted treatment like dapansutrile, which addresses immune activation pathways in Parkinson's without causing general immunosuppression or unwanted side effects. The trial's objectives include evaluating dapansutrile's safety and tolerability, its ability to reduce inflammation in the brain and periphery, and its potential to positively influence clinical symptoms and disease progression.

Olatec Therapeutics, the developer of dapansutrile, is encouraged by the collaboration with Dr. Williams-Gray and the opportunity to advance dapansutrile as a possible disease-modifying treatment for Parkinson's. The company is a clinical-stage biopharmaceutical firm focused on developing oral NLRP3 inhibitors to treat a variety of acute and chronic inflammatory diseases mediated by IL-1.

Parkinson's disease affects over 9 million people worldwide, with no current treatments capable of altering the disease's progression. The condition is characterized by a range of motor and non-motor symptoms, including changes in movement, speech, cognitive decline, mood disturbances, and issues with bladder, bowel, sleep, and blood pressure control.

The scientific rationale behind targeting the NLRP3 inflammasome in Parkinson's disease is based on evidence suggesting that inflammation contributes to neuronal damage and loss in the brain. The NLRP3 inflammasome, activated within brain inflammatory cells called microglia, may be triggered by abnormal α-synuclein protein aggregates. By inhibiting the NLRP3-dependent neuroinflammatory process, dapansutrile could potentially slow disease progression.

Dr. Caroline Williams-Gray is a prominent clinician scientist with a specialization in Parkinson’s disease and movement disorders. Her research underscores the role of the immune system in the variability and progression of Parkinson's, with a particular focus on the impact of peripheral immune activation on neuronal damage in the brain.

Cure Parkinson’s, a UK-registered foundation, is dedicated to funding and facilitating research aimed at finding a cure for Parkinson's. The organization collaborates with other entities to fund clinical trials and has pledged significant financial support to research efforts.

Dapansutrile, the investigational drug in question, is a small molecule that specifically targets the NLRP3 inflammasome, inhibiting the production of inflammatory molecules. It has shown promise in preclinical and clinical models across various disease areas, including Parkinson's and Alzheimer's disease.

Olatec Therapeutics is committed to advancing its platform of NLRP3 inhibitors, with dapansutrile as its lead compound, and has a robust portfolio of intellectual property protecting its compounds. The company's team consists of experienced professionals with expertise in inflammation and immunology, who have been instrumental in the discovery and development of first-line inflammation treatments.