Kiwi scientists are trying to get closer to revealing the important role one gene plays in the development of Parkinson’s disease.

A new study comes after research in New Zealand, supported by the charity of world-renowned Hollywood star Michael J Fox, sheds light on the fascinating link of the gene to the notorious neurodegenerative condition.

Parkinson’s is a progressive neurodegenerative condition caused by a lack of dopamine in the brain, resulting in slow and awkward movements.

Despite decades of research, and its impact on one in 500 New Zealanders and millions more worldwide, the disease remains a medical mystery.

Doctors don’t yet know why most people develop it and for those who are diagnosed, there is no cure.

Over the past few years, scientists have been pursuing promising new clues in the genetic mutation that is one of the biggest risk factors for the disease.

The specific gene involved is called acid beta glucoserebrosidase, or GBA.

Research has shown how GBA mutations inhibit enzymes that help clear out damaged or excess parts of cells, before they can build up to cause the damage seen in Parkinson’s disease.

Last August, a team led by Associate Professor Justin O’Sullivan, from the University of Auckland-based Liggins Institute, published findings that pinpoint the specific components of GBA that play a major role in regulating and delaying the onset of disease.

In the “non-coding” area of ​​GBA – once thought of as aimless “junk” DNA – the team screened 128 sites to find that, where the gene happened to have a specific combination of three short non-coding DNA sequences, Parkinson’s onset could be delayed by five. year.

They also identified six other non-coding regions that act as switches to control how the GBA gene is turned on or off in the brain’s movement and cognitive centers.

Scientists – funded in part by the Michael J Fox Foundation for Parkinson’s Research – are also creating maps showing how such switches affect other genes – apart from GBA – throughout the human body.

In the new study, supported by New Zealand’s Marsden Fund, O’Sullivan will work with University of Otago geneticist Professor Martin Kennedy to further explore the GBA puzzle.

Kennedy said the project proved to be an “accidental amalgamation” of initially separate research.

While O’Sullivan has focused on how gene expression is regulated in different cells, Kennedy and PhD student Oscar Graham has developed a new DNA sequencing method to check for mutations in the GBA gene.

When O’Sullivan and Kennedy sat together at the Queenstown conference to share their work, they realized what they could learn by putting it together.

“When put together, the two data sets show that not only clear mutations in GBA, but also a natural pattern of subtle variations in GBA genes, appear to impact Parkinson’s disease,” said Kennedy.

In addition, this may occur through changing the expression of perhaps 20 to 30 other genes.

Their joint study, which also involved the NZ Brain Research Institute’s renowned clinical director, Professor Tim Anderson, ultimately sought to confirm that subtle genetic changes in GBA do affect Parkinson’s early age.

But they also wanted to know why so many people who carry the GBA mutation don’t develop the disease.

Furthermore, they aim to build simpler ways of detecting variation so that it can be tested in larger studies, along with sophisticated new models exploring its effects in cell biology.

The team plans to import specific stem cells taken from Parkinson’s patients, which will be modified in the laboratory using the latest gene editing methods to provide cells with various forms of the GBA gene.

“These cells can be differentiated in the laboratory into different cell types, such as certain brain cells, then we can see differences in gene expression due to the presence of different forms of the GBA gene,” explains Kennedy.

“Then we’ll set up experiments to better understand the biological impact of differences in expression of any gene, both in cultured cell models, and ultimately in humans.”

Kennedy expects this pioneering research to come up with challenges – particularly around modifying genes in cell lines, but also in understanding what the differences in gene expression caused by different forms of GBA actually mean.

“Until we discover those changes and start thinking about gene function, we won’t be able to plan proper experiments to answer the key questions of this research.”

But if successful, their research may prove important for ongoing efforts to understand and prevent Parkinson’s.

“GBA is the single biggest genetic factor we know of that underlies Parkinson’s, but we don’t really understand how it exerts its effects,” said Kennedy.

“In addition, drugs are being developed and piloted that target the GBA and its lines of operation, so it is increasingly important to understand all the how and why of the GBA.

“We believe our genetic work will lead to a better ability to predict Parkinson’s risk – and possibly allow targeting of treatment, or even prevention for people at high genetic risk who don’t already have it.”