University of Toronto (University Health Network)
Staff neuropathologist, Toronto General Hospital
Pilot Project Grant: $ 44,818
Development of skin biopsy as a diagnostic tool for Parkinson’s disease
Currently, doctors diagnose people with Parkinson’s disease based on symptoms – usually late in the onset of the disease, when the majority
of dopamine-producing brain cells have already died. Even then, clinical diagnoses have an error rate of 10-20 percent.
If researchers develop a test that would definitively diagnose Parkinson’s early, that test would not only help families plan for the future, it could be vitally important once treatments to slow down the disease’s progression are discovered.
At the University of Toronto, Dr. Lili-Naz Hazrati and her colleagues are developing a simple skin biopsy that would diagnose Parkinson’s by analyzing the build up of a protein called alpha-synuclein in the skin and bowel. Clumps of misfolded or abnormal alpha-synuclein have been found in the brains of people with Parkinson’s disease, and the abnormal protein may originate first in the bowel or the skin before moving to the brain.
“We need to detect Parkinson’s disease before it hits the brain, because by the time you get the symptoms of Parkinson’s it has already progressed tremendously and there have been a lot of losses in the brain that are irreversible,” says Hazrati, a pathologist.
Hazrati is using a new staining technique that highlights only the abnormal forms of alph-synuclein in biopsies. She is validating the test with people already diagnosed with Parkinson’s, compared to people who have no signs or symptoms of the disease.
“What we need is a test that’s a clear as a pregnancy test, that’s not difficult to interpret,“she says. “You don’t want to put on someone the burden of having Parkinson’s disease or getting Parkinson’s disease in a few years if you’re not sure. That would be very distressing for people.“
Eventually, such a test might also be used to evaluate the success of any treatment aimed at correcting or preventing the misfolding of the alpha-synuclein protein. If Hazrati`s initial work on the biomarker test is successful, she and her colleagues will conduct a large-scale clinical trial to further test it.
Hazrati has long been fascinated by the molecular changes and organization of the brains of people with Parkinson’s disease. Her goal is to make a firm connection between those changes and the way they affect the lives of people living with the disease.