Cooling 'brains on fire' to treat Parkinson's

1 November 2018

A promising new therapy to stop Parkinson’s disease in its tracks has been developed at The University of Queensland.

UQ Faculty of Medicine researcher Associate Professor Trent Woodruff said the team found that a small molecule, MCC950, stopped the development of Parkinson’s in several animal models.

“We have used this discovery to develop improved drug candidates and hope to carry out human clinical trials in 2020,” Dr Woodruff said.

“Parkinson’s disease is the second-most common neurodegenerative disease worldwide, with 10 million sufferers, whose control of body movements is affected.

“The disease is characterised by the loss of brain cells that produce dopamine, which is a chemical that co-ordinates motor control, and is accompanied by chronic inflammation in the brain.

“We found a key immune system target, called the NLRP3 inflammasome, lights up in Parkinson’s patients, with signals found in the brain and even in the blood.

“MCC950, given orally once a day, blocked NLRP3 activation in the brain and prevented the loss of brain cells, resulting in markedly improved motor function.”

There are no medications on the market that prevent brain cell loss in Parkinson’s patients, with current therapies focusing on managing symptoms rather than halting the disease.

UQ Institute for Molecular Bioscience researcher Professor Matt Cooper said drug companies had traditionally tried to treat neurodegenerative disorders by blocking neurotoxic proteins that build up in the brain and cause disease.

"The problem is that if one toxin is blocked by a drug, another may still build up and cause disease. In contrast, our line of research focuses not on individual toxins, but instead on the immune cells in our brains that clear amyloid and other neurotoxins. 

"These cells, called microglia, normally protect us from infections that can lead to encephalitis and meningitis. However, as we age, our immune system can become overactivated, which leads to neuroinflammation. Over-active microglia can no longer function as efficient 'cleaners' of neurotoxins, but instead contribute to long-term damage in the brain.

“MCC950 effectively ‘cooled the brains on fire’, turning down microglial inflammatory activity, and allowing neurons to function normally.”

The study is published in Science Translational Medicine (DOI: 10.1126/scitranslmed.aah4066), and was made possible by generous support from the Michael J. Fox Foundation for Parkinson’s Research and Shake it Up Australia Foundation, which fund innovative research into therapies for Parkinson’s disease.

Dr Kuldip Dave, Director of Research Programs at The Michael J. Fox Foundation, said, "Inflazome has validated a promising new target for a promising new target for Parkinson’s therapeutics and translated that finding into a potential drug to treat Parkinson’s disease. This is a key aspect of The Michael J. Fox Foundation’s research strategy, and we look forward to their candidate drug’s continued development.”

Clyde Campbell, Founder and CEO of the Shake It Up Foundation, said, “Shake It Up is proud and excited to be a part of the collaboration’s funding team, allowing highly-talented researchers an opportunity to create world leading breakthroughs that have the opportunity to be a game changer for people with Parkinson’s."