How Gene Networks Regulate the Risk of Parkinson's

There’s new hope for treating Parkinson’s disease with the publication of groundbreaking genetic research from the University of Auckland, New Zealand.

The study is authored by a research team, led by Professor Justin O’Sullivan from the University’s Liggins Institute and Professor Antony Cooper of the Garvan Institute of Medical Research.

In a paper  published in the journal Brain, the research team took 90 known genetic changes that are each individually associated with the risk of developing Parkinson’s disease and showed how they affect biological pathways in the body’s tissues, many far from the brain. Nine of these pathways, some of which have not been linked to Parkinson’s before, seem to be key.

“Our ultimate aim is to slow or stop Parkinson’s,” says Justin. “If we can understand how the genetic changes work together to contribute to the risk of developing the disease, we’ve got a shot at doing that.

“Eventually, personalised medicine will allow for people to be treated for the exact form of Parkinson’s that they have – or are at risk of developing. We’re working for that day to come as quickly as it can,” he says.

The findings improve scientists’ understanding of genetic risk factors for developing Parkinson’s disease.

“Our intent is to identify which of the 90 genetic changes interact in specific combinations that disable a biological pathway, and thereby contribute to an individual developing a disease subtype - and this paper is a critical first step (towards that goal),” says Antony.

Sophie Farrow conducted the study as part of her PhD. In a follow-up study, funded by The Michael J. Fox Foundation for Parkinson’s Research, Sophie is now moving from computers to lab work on human cells to test the team’s theory and prove the genetic variations have the effect they have identified.

In August 2020, the leading journal on Parkinson’s, Movement Disorders, featured the team’s findings as a cover story, after they showed that genetic changes in a gene called GBA play a significant role in regulating the age of onset of the disease.

One of the team’s latest pieces of research (published in Frontiers in Genetics in 2022) suggests that changes within a part of the heart called an atrial appendage could contribute to people developing Parkinson’s.

“Parkinson’s was once seen solely as a disease of the brain, but now we know it’s much, much more than that,” says Justin.

Despite the number of people it affects, Parkinson’s remains a medical mystery.

Doctors do not know why most people develop the disease and there is no cure.

More than 10 million people are living with Parkinson’s worldwide, and about 1-in-100 people over the age of 60 in New Zealand have the condition, with symptoms including tremor, rigidity, fatigue, bladder and bowel problems, depression, and sweating.

Reference: Farrow SL, Schierding W, Gokuladhas S, et al. Establishing gene regulatory networks from Parkinson’s disease risk loci. Brain. Published online January 30, 2022:awac022. doi:10.1093/brain/awac022

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