New UK trial to test Olatec’s dapansutrile in early Parkinson’s
Treatment could ease symptoms, slow disease progression
Olatec Therapeutics will launch a Phase 2 clinical trial in the U.K. to investigate the potential of oral dapansutrile to slow or stop Parkinson’s disease progression by reducing inflammation in the brain.
The study, made possible by a grant from the U.K.-based Cure Parkinson’s, will begin in mid-2024, enrolling about 36 participants with early Parkinson’s. It will take place at the John van Geest Centre for Brain Repair at the University of Cambridge, under the direction of Caroline H. Williams-Gray, PhD, who leads the Cambridge Parkinson’s Disease Research Clinic.
“In this trial, we aim to determine dapansutrile’s safety and tolerability in patients with Parkinson’s, and to establish whether treatment with dapansutrile can reduce inflammation in both the brain and periphery in Parkinson’s,” Williams-Gray said in an Olatec press release. “We will also investigate whether this results in a positive effect on clinical symptoms and disease progression.”
Parkinson’s is thought to be caused by the buildup of toxic protein clumps, called aggregates, that contribute to the progressive death of dopamine-producing neurons in the brain. The resulting drop in dopamine levels leads to not only the disease’s hallmark motor symptoms, like slow movements and tremors, but also nonmotor symptoms, such as cognitive impairment.
While standard treatments like levodopa can relieve symptoms, there are no therapies that can alter Parkinson’s progression.
‘Pressing need’ for targeted treatment
Growing evidence suggests the accumulation of protein aggregates triggers an inflammatory response, resulting in further damage and neuron loss. The immune response is driven by the NLRP3 (a protein that leads to brain inflammation) inflammasome, a multi-protein complex that normally detects cellular threats.
Dapansutrile is designed to access the central nervous system — which is comprised of the brain and spinal cord — block NLRP3, and prevent inflammasome formation. The goal is to selectively reduce Parkinson’s-related inflammation and slow disease progression without overly suppressing the immune system.
“There is a pressing need for a specific treatment, such as dapansutrile, which targets the most relevant aspects of the immune activation pathway in Parkinson’s without causing general immunosuppression and leading to unwanted side effects,” Williams-Gray said.
In clinical trials involving people with other NLRP3 inflammasome-mediated conditions, the investigational therapy was generally safe and well tolerated, according to the company.
There is a pressing need for a specific treatment, such as dapansutrile, which targets the most relevant aspects of the immune activation pathway in Parkinson’s without causing general immunosuppression and leading to unwanted side effects.
In the U.K. trial, patients with early Parkinson’s will receive either dapansutrile or a placebo for six months, followed by an optional, six-month open-label extension phase. In an open-label study, both participants and researchers know the exact medication patients are given.
The study will assess dapansutrile’s impact on brain inflammation and disease progression, as well as its safety and tolerability.
Damaris Skouras, Olatec’s founder and CEO, said the grant “provides the possibility to advance dapansutrile in its first [central nervous system] indication as a potential disease-modifying treatment for Parkinson’s.”
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