Drug Molecule Targets Early-Onset Parkinson’s Disease

More than 100,000 Canadians currently live with Parkinson’s disease. A novel drug molecule being studied by researchers from McGill University could reactivate housekeeping functions in brain cells of young Parkinson’s patients, paving the way for potential future treatments for this incurable, degenerative disease.

“We are excited about this drug compound because it raises the possibility of a cure for Parkinson’s disease for a subset of patients,” said Kalle Gehring, a biochemistry professor at McGill University.

Developed by the biotech company Biogen, the new compound has shown promising results activating parkin, a key protein in the brain responsible for “cleaning up” and recycling damaged mitochondria – the energy powerhouse of the cell. When parkin doesn’t work properly, these damaged mitochondria accumulate, leading eventually to Parkinson’s disease.

In studies published in 2013 and 2018, Gehring shed light on the functions of parkin based on data collected at the Canadian Light Source (CLS) at the University of Saskatchewan (USask).

In this new follow-up study, Gehring used the CMCF beamline at the CLS to determine how the Biogen compound activates parkin. They found that it glues together parkin and a natural activator present in the cell. This molecular-level information is essential for the drug's future development.

“The way the drug molecule turns on parkin is through a secondary route, which is effective for specific mutations of parkin that occur in younger patients,” he said.

After turning proteins into tiny crystals, Gehring and his team used a technique called protein crystallography to identify their 3D structures and learn where the novel drug binds and how it affects the proteins. The results are published in the journal Nature Communications.

“We need quality data to solve the protein structures and see their 3D pictures. It takes a facility like the CLS to take Canadian research to an international level,” said Gehring.

While Parkinson’s symptoms – slowed movements, tremors, and balance problems – often appear in people in their 60s, onset at an earlier age is not uncommon and five to 10 per cent of people diagnosed are affected before they turn 40.

“The hope is that one day we’ll find compounds that can treat Parkinson’s disease in general,” said Gehring. “As the population in Canada is aging and better treatments for other diseases are becoming available, neurodegenerative diseases such as Parkinson’s will be a major health concern.”

While Gehring will keep studying the pathways of parkin activation as part of his ongoing research about understanding the causes of Parkinson’s disease, it will be up to Biogen to apply the results of this new study in future drug development, he said.

Reference: Sauvé V, Stefan E, Croteau N, et al. Activation of parkin by a molecular glue. Nat Commun. 2024;15(1):7707. doi: 10.1038/s41467-024-51889-3

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