Repurposed Therapies, New Compounds to Be Tested to Block Brain Inflammation in Parkinson’s

Researchers in Australia are planning to test therapies already being used in other inflammatory conditions, as well as new compounds, for their potential to block brain inflammation and halt Parkinson’s disease progression.

Conducted by researchers at The University of Queensland (UQ) in Australia, the study, “Pharmacological Targeting of Inflammasome Activation Mechanisms in Synuclein Models of Parkinson’s Disease,” is made possible by a two-year research grant funded by The Michael J. Fox Foundation for Parkinson’s Research and Shake It Up Australia Foundation.

Queensland researchers had previously found evidence supporting the activation of an immune system complex called the inflammasome in chronic inflammation and loss of brain cells in Parkinson’s. They also found a new signaling pathway through which toxic forms of the protein alpha-synuclein — the main component of the Parkinson’s hallmark Lewy bodies — activate the inflammasome.

The scientists also showed that this pathway is activated in isolated immune cells from Parkinson’s patients and in preclinical models of the disease. These preclinical experiments also revealed that blocking the pathway with a repurposed therapy — which refers to treatments already approved by regulatory agencies for other indications — was beneficial.

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“In our previous study, we were trying to ‘cool brains on fire’ from inflammation whereas this time we’re focusing on stopping that fire from starting in the first place,” Richard Gordon, PhD, a group leader at the UQ Centre for Clinical Research who will be leading the research, said in a press release.

The team will now assess a new therapeutic strategy to slow or halt Parkinson’s progression by blocking chronic activation of the immune system and brain inflammation.

They will be testing a set of more effective and targeted compounds, both new and repurposed, intended to block the activation of the inflammasome in preclinical models. If effective, the study will provide the basis for clinical trials in patients, according to the researchers.

“If we can prove they work in treating Parkinson’s disease, we can repurpose these and get them to the clinic to treat patients faster than developing new drugs,” Gordon said.

“Brain inflammation is a key area of Parkinson’s research,” said Clyde Campbell, Shake It Up Australia’s founder and CEO, adding that new treatments “can rapidly progress to clinical trials” through the Queensland Drug Repurposing Initiative, a UQ partnership with the Cure Parkinson’s Trust and the international Linked Clinical Trials Initiative, funded by the Advance Queensland program and Shake It Up Australia.