OTTAWA — High cholesterol levels predict heart disease. High blood-sugar levels can predict diabetes. But no single test exists to predict who will develop Parkinson's disease, the second leading brain-wasting disorder behind Alzheimer's.
Now, a decade-long effort which started at Harvard University and continued in Ottawa, has yielded a method that, in principle, could identify people at risk of developing a disease that afflicts an estimated 150,000 Canadians.
The story behind this finding shows why progress toward preventing or curing Parkinson's has been so slow. It also highlights how recent advances in Alzheimer's research served as a model for what some researchers have already dubbed "the Ottawa test" for Parkinson's.
The disease is defined by the death of brain cells that produce dopamine, a chemical messenger between nerve cells. It's the loss of dopamine-producing nerve cells that lead to Parkinson's symptoms of rigidity, poor balance and uncontrollable shaking.
Currently, the lack of a definitive test means physicians only reach a diagnosis by testing for — and eliminating — other diseases that can cause the same symptoms. Patients are also assessed according to the severity of those physical symptoms. But the method is so imprecise that it can lead to diagnosis only when the disease is already well advanced.
An international team led by Dr. Michael Schlossmacher, a neuroscientist at the Ottawa Hospital Research Institute, believes it has identified signature proteins in the blood and spinal fluid that show the progression of Parkinson's in the brain.
The findings, presented last month at the World Parkinson's Congress in Scotland, require further testing. But if proven, the protein markers could form the basis of a test to screen people for early signs of the disease.
It might also allow scientists to study how the disease progresses and, perhaps, find drugs to slow or halt the process.
"We in (the) Parkinson's (field) are still stuck in the old days, where it's only the clinical impression and examination that determines whether this is Parkinson's or not," said Schlossmacher, who's also the Canada research chair in Parkinson's at the University of Ottawa.
"We have to move forward to laboratory-based measurements that are more objective than subjective."
His research has attracted $40 million from the Michael J. Fox Foundation, which is funding a five-year study of a spinal-fluid test to detect Parkinson's, developed by Schlossmacher and his collaborators in Germany and the United Arab Emirates.
Up to 700 patients with advanced Parkinson's are expected to be enrolled in Canada, the U.S. and Europe. The large-scale trial would allow physicians and scientists from around the world to verify the accuracy and effectiveness of the test independently.
Spinal taps, which involve inserting a needle into the lower back and withdrawing a small amount fluid, have drawbacks. Many doctors and patients are nervous about the procedure, which they fear will be painful and cause headaches, infection, or nerve damage.
For that reason, Schlossmacher's team is also at the early stages of developing a blood test for Parkinson's, a much less invasive procedure. The experimental blood test has so far been tried in nearly 600 patients in Canada and the United States.
Both tests aim to measure a telltale Parkinson's protein known as alpha-synuclein, which is found at abnormally low levels in the spinal fluid of seven out of 10 patients with the disease — because, researchers believe, once it's in a person's nervous system, it collects in the brain in deposits that damage neurons and lead to the debilitating symptoms of Parkinson's.
Some people have a genetic predisposition to high alpha-synuclein levels, and a blood test could look for high levels of the protein in the blood, where it would be detectable long before it began causing symptoms.
But because at least 15 per cent of patients with the disease don't appear to have elevated levels of alpha-synuclein, the protein is not necessarily a definitive test. Indeed, it remains to be seen how many people who have it actually end up with the disease. But that is part of the research project.
The idea for a Parkinson's diagnostic test emerged nearly 20 years ago, when Schlossmacher was a post-doctoral fellow at Harvard.
As a young researcher working with Dennis Selkoe, a leading Alzheimer's expert, Schlossmacher was assigned to look for the signature proteins that could be responsible for Alzheimer's.
In 1992, Schlossmacher was the lead author of a paper that, for the first time, identified a protein called beta-amyloid as a physical hallmark of Alzheimer's — a discovery that became the cornerstone of what is today a leading theory about how to treat the disease.
He recalled how Selkoe had urged him to branch out, saying: "You know, Parkinson's is 10 years behind Alzheimer's. Why don't you look into it?"
"It was my work there, in a very junior role, that inspired me to pursue Parkinson's and become a neurologist," Schlossmacher said.
In 2001, after completing his neurology training, Schlossmacher took his mentor's advice and began zeroing in on alpha-synuclein as one of the proteins that likely plays a key role in Parkinson's. In 2006, after leaving Harvard, Schlossmacher refined his research in Ottawa.
He said the next four years could decide whether real progress is made in Parkinson's diagnosis. "By then, we'll know whether it's really exciting and useful, or whether it was just a good idea."
BY PAULINE TAM, OTTAWA CITIZEN
Tuesday, October 19, 2010
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