Revealing the culprit behind Parkinson’s disease

An estimated 55,000 Canadians are living with Parkinson’s disease. While researchers are advancing therapies to treat symptoms, such as tremors, there is currently no method to stop progression.

To begin addressing this problem, a team of scientists at Lawson Health Research Institute is developing an imaging tracer. 

“There’s a protein in the brain called alpha-synuclein (α-syn) that scientists believe is a culprit in causing Parkinson’s disease. The protein forms in ‘clumps’ called Lewy bodies that kill brain cells and potentially lead to disease,” explains Dr. Justin Hicks, Lawson Imaging Scientist. “Unfortunately, we have no way to study it in human brains and this has limited our ability to test therapies against it.”

Efforts have been made to study the elusive protein through modern imaging techniques like positron-emitting tomography (PET). Scientists have attempted to develop a PET probe – a radioactive molecule that targets the specific protein in order to produce highly specific images or scans – but they have been unsuccessful.

Above: Dr. Justin Hicks working in the Nordal Cyclotron & PET Radiochemistry Facility

“Unfortunately, the Lewy bodies caused by α-syn are hard to distinguish from protein clumps found in Alzheimer’s disease and other dementias. This makes it very difficult to know whether a PET probe has found clumps associated with Parkinson’s disease.”

Through a new study, Dr. Hicks and his team are working to find a solution. To do so, they will examine a different but related protein.

“There’s another protein called fatty acid binding protein 3 (FABP3) and one of its roles is to ‘chaperone’ the α-syn protein in human cells. Past studies have shown that levels FABP3 are higher in patients with Parkinson’s disease when compared to healthy controls,” explains Dr. Hicks. “This suggests that high concentrations of FABP3 can be used as an alternate measure of α-syn.”

They hope to measure levels of the FABP3 protein in place of the α-syn protein, and gain a better understanding of the role that both proteins play in the development and progression of Parkinson’s disease. To image Lewy bodies associated with Parkinson’s disease, the researchers are working to produce a PET probe that targets FABP3.

To accomplish this, they will be working in their lab to find a chemical that targets FABP3. Once found, they will attach a radioactive isotope to the chemical and produce a finished tracer. The tracer will then be tested in preclinical models. 

Once injected, the PET probe will find and stick to FABP3. The PET isotope will emit a small amount of radioactivity and these emissions will show up as PET images.

“The ultimate goal is to develop a PET probe that can be used to distinguish Parkinson’s disease from other neurodegenerative diseases. The probe could also be used to assess new therapies that reduce levels of the α-syn protein,” says Dr. Hicks. “If successful, we hope this research will lead to a better understanding of the progression of Parkinson’s disease and ways to prevent it.”

Dr. Hicks and his team are being funded for this project through Lawson’s Internal Research Fund (IRF) competition. “Lawson’s IRF is extremely important for early career researchers. It allows us to generate data and publications to then apply for larger external funding. It also permits an added level of risk to pursue projects that may not reach their end goal but often spur new lines of research.”

Above: A graphic depiction of this research project and its goals.