Designing new drugs for Parkinson’s disease
Structure-based design of small-molecule activators of Parkinson's
In brain cells that function normally, a protein called Parkinson plays a critical role. It recycles excess or defective material, including damaged mitochondria, the energy-producing powerhouse in cells.
When Parkinson isn’t working, clumps of damaged mitochondria and proteins accumulate in brain cells and kill them. The death of those cells, especially those that produce the crucial signalling chemical dopamine, cause inherited forms of Parkinson’s disease.
At McGill University, neuroscientist Simon Veyron, a post-doctoral fellow, is designing new drugs to interact with Parkin.
“I’m trying to develop a new drug that will activate Parkinson in order to slow down progression of the disease,” he says.
If Veyron can find or create a compound that binds to Parkin and helps it resume its recycling function, that could prevent the death of the crucial dopamine-producing cells.
Veyron is using biochemistry and crystallography to recreate and study the structure of Parkinson at the atomic level. He has also screened thousands of drugs and other compounds to find ones that are a good fit with Parkinson – literally.
“I’m trying to develop a new drug that will activate Parkinson in order to slow down progression of the disease.”
He’s combining fragments from these drugs and then sticking them to the protein in a specific place, called the inhibiting pocket.
“If we place something in this inhibiting pocket, it will lead to activation,” he says.
Positioning the new substance in exactly the right place in the inhibiting pocket is crucial for success. Putting the new substance on the wrong side of the pocket, for example, could fail to activate Parkinson.
“It’s like a puzzle where we have to first create the pieces, so it’s really hard,” he says.
If Veyron is successful, the compound he creates could eventually form the basis of one or more drugs to treat Parkinson’s.
Veyron, who is from France, had initially wanted to become a medical doctor. His career goals changed during his first year of university in Paris, when he began an internship with a biochemistry professor.
“When I stepped into the lab and I did my first day, I knew it was for me. It was amazing,” he says of the research.
By working in the Parkinson’s field, Veyron can now combine his love of research with his desire to help people struggling with the effects of disease.
“I’m really lucky to love what I’m doing at work,” Veyron says.
How your support made this research project possible
This grant from Parkinson Canada will allow Veyron to stay in Canada for at least another year to pursue his research. He’s the only person in the lab working on structure-based design of these molecules to activate Parkinson, so the grant plays a central role in attracting international scholars and researchers like Veyron to Canada.
Veyron’s message to potential donors is to remember the essential role of research.
“Without research, we will never make progress in science,” he says. “Parkinson’s disease and a lot of other diseases are something we have to study in order to comprehend and then treat them. It’s amazing that people donate to these organizations, because without them, research could not happen.”
The pandemic has made non-COVID research particularly challenging, he says.
“A lot of research had to stop because we do not have enough money and not enough help from the government,” he says.Donate to fund more research projects