December 02, 2020
A team of Simon Fraser University researchers developing a drug design approach that could lead to new disease-modifying therapeutics for diseases such as Parkinson’s have been awarded a $1 million grant from the Canadian Institutes for Health Research.
Led by professor of chemistry Andrew Bennet, the team – which also includes SFU’s David Vocadlo, Rob Britton and University of Manitoba’s Brian Mark – hopes to develop the first treatment that can alter the course of the disease and stop its progression, rather than just treating the symptoms.
Parkinson’s has been linked to deficiencies in an enzyme called glucocerebrosidase, which is critical to breaking down waste products in the body into more easily metabolized components like glucose and ceramide, a type of fat. However, genetic mutations associated with this enzyme can result in an unstable structure and a loss of function that can cause damage to the body and contributes to the progression of Parkinson’s disease.
The approach of Bennet’s team is to design small molecules that form a chemical bond to the mutated enzyme, acting as a mannequin, mimicking the enzyme’s natural substrate, and “tricking” glucocerebrosidase into folding around the small molecules like a suit. Once its job is done, the molecules break off from the tailored enzyme, allowing it to be “worn” by other molecules in the body and once again perform its critical role of breaking down waste.
The economic cost of Parkinson’s disease alone is estimated at $14.4 billion annually in the US and its prevalence is predicted to more than double by 2040. Current therapies treat the symptoms of the disease, but do not alter the disease course. Identifying new disease-modifying therapies is a critical, unmet need. The fundamental chemical biology studies underway by this research team promises to yield key insights and tools that will enable the biotechnology sector to develop disease-modifying therapeutics for Parkinson’s disease and the many other so-called lysosomal storage disorders.