Screening genes to find the cause of Parkinson’s

Researchers trying to find the cause of Parkinson’s disease are placing much of the blame on a prodigious protein called alpha-synuclein.

When too much of this protein clumps up in the brain cells that produce dopamine, a brain chemical that helps cells communicate with one another, those critical neurons die, and Parkinson’s results.

Researchers don’t know exactly why alpha-synuclein clumps up or what other proteins might be involved in the complicated process that causes alpha-synuclein to malfunction and kills neurons.

At McGill University, Thomas Goiran, a neuroscientist and postdoctoral fellow, is using a gene-editing tool called CRISPR to search for other genes and proteins that might be involved in triggering alpha-synuclein to misbehave and causing dopamine-generating brain cells to die. Goiran’s research is made possible through a Basic Research Fellowship from Parkinson Canada National Research Program for $100,000 over 2 years.

“Even if we know what happens in Parkinson’s disease, we don’t really know how it happens,” Goiran explains. “My project is to identify these other actors involved in this neuronal death.”

Goiran will inject engineered stem cells with clumps of alpha-synuclein and then use the CRISPR technology to screen those cells to identify which genes are important for the process of cell death that results.

“We’ll see whether the cells die or not when different genes are knocked out,” he says.

Ultimately, he hopes his work will produce a target for gene therapy that can either activate genes and proteins that are not working enough, or block those that are too active and contribute to the death of the dopamine-producing cells. Identifying additional genes involved in the process of allowing alpha-synuclein buildup could also result in a biomarker – a test to determine who is at risk for Parkinson’s disease.

Goiran, who began his research on brain disorders in his native France, is fascinated by the connections between brain cells and how those connections work. He wanted to explore the similarities and differences between brain tumors and neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. He specialized in his current research on Parkinson’s disease hoping that previous fundamental research will eventually help to produce better treatment for people with Parkinson’s.

“Why are there genes in the brain that become toxic? I want to better understand that,” he says.