Research team proposes new system to classify Parkinson’s disease
To advance the development of more tailored treatments of Parkinson’s disease, scientists must first develop a classification system for the disease that uses biological features — not just clinical symptoms.
So argues a team of researchers led by Anthony Lang, a principal investigator at the University of Toronto’s Tanz Centre for Research in Neurodegenerative Diseases.
“This is a complex group of disorders that may cause similar symptoms, but biologically they're very different,” says Lang, also the Jack Clark Chair for Parkinson's Disease Research at U of T’s Temerty Faculty of Medicine and the Lily Safra Chair in Movement Disorders at University Health Network.
“If we cannot find ways to subdivide patients biologically, then applying a therapy designed to affect one biological pathway may not be effective in another group of patients that doesn't have that same pathway involved — and we won’t really have precision or personalized medicine for Parkinson’s disease.”
Currently, Parkinson’s disease is classified based on clinical presentation and symptoms, but the disease may affect the brain for years, possibly even decades, before symptoms appear. If future therapies can treat the underlying disease, not just the symptoms (known as disease-modifying therapies), patients will need to receive the treatment early and the treatments will vary according to the biology of the disease.
Similar approaches are used for other diseases. Cancer treatments vary not only by tumour site but also based on the molecular features of a tumour. Alzheimer’s disease researchers have also recognized the biological mechanisms involved in the disease and are starting to develop different drugs that target different mechanisms.
In a paper published in The Lancet Neurology earlier this year, Lang and other researchers from Canada, the United States and Europe proposed a biological classification system for Parkinson’s disease, called SynNeurGe.
Their proposed system classifies the disease based on three main biomarkers: the presence or absence of misfolded alpha synuclein protein, which clumps together and is believed to cause or contribute to the underlying neurodegeneration; evidence of neurodegeneration using specific imaging techniques; and presence of gene variants that increase the risk of Parkinson’s disease.
The classification also considers whether clinical features are present. The different combinations of biomarkers classify the disease into various subtypes.
Lang says that research by Tanz Centre researchers has contributed significantly to the body of knowledge used to develop their proposed biological classification. For example, Ekaterina Rogaeva’s research on the genetics and epigenetics of Parkinson’s disease has shown that multiple genes and environments can influence Parkinson’s risk, highlighting the need to tailor therapies based on a patient’s genetic makeup.
Other Tanz Centre researchers, including Anurag Tandon, Joel Watts, Martin Ingelsson and Gabor Kovacs, have been studying the role of misfolded alpha synuclein in neurodegeneration as well as cases of Parkinson’s disease where alpha synuclein is absent, which informed how the team included alpha synuclein in the classification.
“Dr. Lang and his team have published a landmark paper that will greatly aid with the discovery of the causes of Parkinson’s disease and will eventually impact clinical practice,” says Graham Collingridge, director of the Tanz Centre. “I am delighted that our researchers have played such a key role in this important biological classification.”
Currently, Lang and the paper’s co-authors argue that such a classification should only be used for research, though eventually it will almost certainly have clinical applications. For now, more research is needed on the biomarkers, how they should be interpreted and what they mean for patients.
“Eventually we will see a biological approach influencing clinical care, particularly when we finally have effective disease-modifying therapies,” says Lang. “We currently don’t know how important these biomarkers actually are. We need large-scale prospective studies of biomarkers, imaging and clinical features to interpret the results, give patients accurate information about their diagnosis and provide appropriate treatment.”
Lang’s team plans to start conducting such studies of cerebrospinal fluid, skin and blood to look for biomarkers of different subtypes of Parkinson’s disease that will help inform the classification system and the development of tailored therapies.
In the meantime, he says that it is important for the Parkinson’s research community to work together to tackle this issue.
“Everybody in the Parkinson’s research community agrees that this area is very important, and we are seeing a rapid development of biomarkers for the disease,” says Lang. “Now is the time to think about these diseases not solely based on their clinical manifestations, but to look at the biology and try to separate different biological subtypes so we can ultimately improve treatment for this disease.”
