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

brain inflammation

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.

“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.

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World War II Chemical Weapon Antidote May Also Fight Parkinson’s, Researchers Suggest

dimercaprol for Parkinson's

Dimercaprol, an antidote to a World War II chemical weapon, was shown to be effective in removing a neurotoxin associated with Parkinson’s, revealing it as a possible treatment for the neurodegenerative disease.

Purdue University researchers report that the antidote can safely and effectively remove acrolein, a neurotoxic substance, from the body. Earlier this year, the researchers from the laboratory of professor Riyi Shi, MD, PhD, published their results on the chemical warfare antidote as a potential Parkinson’s treatment in the Journal of Neurochemistry.

Acrolein is a neurotoxin generated in the body after nerve cells are damaged and is directly linked to Parkinson’s disease. Exposure to acrolein increases pain and triggers a cascade of biochemical events thought to increase the severity of Parkinson’s and other neurodegenerative diseases.

The researchers administered dimercaprol to rats with increased levels of acrolein and nerve damage, a model applicable to Parkinson’s disease, and tested the ability of dimercaprol to block acrolein and neurodegenerative disease progression.

They observed that dimercaprol neutralized acrolein and eliminated it from the brain. Importantly, adding dimercaprol led to an increased survival rate of neurons, improved mobility, and less pain. They also demonstrated that dimercaprol could effectively neutralize acrolein in human cells.

Dimercaprol has several advantages over other chemicals that isolate and eliminate acrolein, including fewer side effects and being easily processed by the body and eliminated via the urine.

“Our studies show that by removing the toxin (acrolein) from the brain, we are not just reducing the symptoms of Parkinson’s disease but also significantly reversing the damage of Parkinson’s disease. This could actually provide a new treatment for Parkinson’s patients,” said Shi, a professor of neuroscience and biomedical engineering in Purdue’s Department of Basic Medical Sciences, College of Veterinary Medicine, and Weldon School of Biomedical Engineering.

Dimercaprol is already approved by the U.S. Food and Drug Administration to treat heavy metal poisoning, so it is known to be safe when administered to humans. Future clinical trials are necessary to test the effectiveness of dimercaprol as a treatment for patients with Parkinson’s and other neurodegenerative diseases.

“We believe that the drug’s classification and method of administration are what make it an attractive therapy option,” Shi said. “By systematically injecting the antidote drug directly into the abdominal cavity, it can be absorbed by the bloodstream and then travel to the brain, where the disease is most harmful and where the drug can most benefit the patient.”

The research was funded by grants from the National Institutes of Health, the Indiana State Department of Health, and the Indiana CTSI Collaboration in Biomedical Translational Research Pilot Program.

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