Michael J Fox Foundation gives $221,000 to NZ hunt for new Parkinson’s drugs

The Michael J Fox Foundation, founded by the Canadian actor and writer, is the world’s largest non-profit funder of Parkinson’s research, and is dedicated to accelerating a cure for Parkinson’s disease and improved therapies for those living with the condition.

Worldwide, an estimated six million people – including 10,000 in Aotearoa New Zealand – live with the condition, which has no cure. Parkinson’s disease is a neurodegenerative disorder that progressively erodes a person’s mobility and quality of life. By the time symptoms are apparent enough for diagnosis, the damage to the brain is too extensive to repair.

“Current treatments only alleviate symptoms but do not target the actual cause,” says Dr Victor Dieriks from the University of Auckland-based Centre for Brain Research, co-lead of the research team.

“What we are seeking is treatments that would delay or even prevent degeneration by targeting the earliest disease processes. One of these early processes is inflammation of brain cells, called ‘neuroinflammation’, and that’s what we are focusing on.”

Neuroinflammation is when cells that usually clean up waste and debris, or fight off infection, become activated for long periods of time, which leads to an attack on healthy brain tissue.

The new project will bring together two strands of research at the centre: one looking at neuroinflammation in brain disorders, including in Parkinson’s disease, the other investigating the actions of alpha synuclein (a-SYN), the problem protein that forms clumps in the brains of people with Parkinson’s disease.

Study co-lead Professor Mike Dragunow and his team at the centre had already discovered that inflammation occurs not only in brain immune cells called microglia – most commonly studied in Parkinson’s - but also in the cells that line the blood vessels throughout the brain, which regulate blood flow and the permeability of the blood-brain barrier.

It is these cells, called pericytes, which may hold the key to a new treatment avenue, and shed light on how a-SYN is involved in degeneration.

The researchers will first determine exactly how a-SYN acts on pericytes (sourcing a pure form of the protein from a collaborator in France). They will test this on pericyte cells isolated from donors with Parkinson’s disease and from people without brain disease, which are held in the Hugh Green Biobank at the centre; and in tissue sections from these same people held in the Neurological Foundation Human Brain Bank, also based at the centre. The team’s access to both brain cells and tissues from the same patients gives them a unique edge.

“If we find that a-SYN causes an inflammatory response in pericytes, then we will test pericyte anti-inflammatory compounds (recently discovered in Professor Dragunow’s laboratory) to see if they have protective effects on cells from people with Parkinson’s,” says Dr Dieriks.

“This could prove the first step towards a new drug therapy that could slow down the progression of the disease early on, before the more debilitating effects set in.”

Professor Dragunow says the Hugh Green Biobank is a huge asset in this project. Established in 2011 with funding from the Hugh Green Foundation, the biobank is dedicated to identifying new treatments for brain disorders by growing and studying human brain cells derived from autopsy and neurosurgical brain tissue donors, including those with Parkinson’s.
He says, “We are immensely grateful for The Michael J Fox Foundation grant, and most importantly to the generous patients and their families who donate tissue for our research. Our hope is that it will one day lead to real improvements in the lives of those affected by this disease.”

The other study investigators are Professor Maurice Curtis, Dr Helen Murray, Dr Deidre Jansson, and PhD student Taylor Stevenson, who with Dr Justin Rustenhoven (now based at the University of Virginia) made the first observations, in Professor Dragunow’s laboratory, of the actions of a-SYN on human brain pericytes. Results are expected by early 2022.

The grant was made to the University of Auckland’s For All Our Futures Campaign, which is raising funds to address major issues affecting New Zealanders. Essential funding also comes from the Hugh Green Foundation (which funds the Hugh Green Biobank), the Health Research Council of New Zealand, Neurological Foundation (which funds the Human Brain Bank), Neuro Research Charitable Trust, and Ian and Sue Parton.