An international research team led by Krembil Brain Institute Senior Scientist Dr. Anthony Lang has proposed a new model for classifying Parkinson's disease (PD).
In recent decades, researchers have uncovered several biological factors that underlie PD. Key factors include a build-up of the protein α-synuclein in the brain, which leads to neuron degeneration, and genetic factors that increase one’s risk of developing the disease. They have also begun to develop reliable methods to test for these factors—called disease biomarkers—in living patients.
Despite these advancements, doctors still diagnose the disease based on clinical features, such as the presence of tremors and other common motor symptoms.
According to Dr. Lang, a Professor of Neurology, the Jack Clark Chair for Parkinson's Disease Research at the University of Toronto and the Lily Safra Chair in Movement Disorders at UHN, this traditional approach to diagnosing PD does not account for the complex biological processes at play.
“We need a radically different way of looking at this disease,” he says. “We have reached a point where our research must be driven by biological determinants of the disease, rather than limited clinical descriptions of its signs and symptoms.”
In a recent article published in Lancet Neurology, Dr. Lang’s team proposed a new, biologically based model for classifying PD—called SynNeurGe (pronounced “synergy”).
The model emphasizes the important interactions between three biological factors that contribute to the disease:
- the presence of pathologic α-synuclein in the brain (S)
- evidence of neurodegeneration, which occurs as the disease progresses (N)
- the presence of gene variants that cause or strongly predispose a person to the disease (G).
According to the team, this “S-N-G” classification system better accounts for the biological heterogeneity of PD and the many ways the condition can present in patients. Consequently, the system could help researchers identify subgroups of patients that have distinct disease processes and develop clinically meaningful disease-modifying therapies.
“We need to recognize that PD can differ dramatically between patients. We are not dealing with a single disorder,” explains Dr. Lang. “Our model provides a much broader, more holistic view of the disease and its causes.”
The team is confident that this new way of looking at PD will help researchers study its molecular basis, distinguish it from other neurodegenerative conditions that share common biological features and identify targets for new therapies.
Despite the model’s potential clinical applications, Dr. Lang cautions that it is intended for research purposes only and is not ready for immediate application to patient care.
Although more research is needed before the classification system can be applied clinically, it is already spurring hope among patients and the medical community.
“The ability to tailor treatments improves when you can identify exactly what is going on in a specific patient like me,” says Hugh Johnston, Founding Chair of the Patient Advisory Board of the Movement Disorders Clinic at the Krembil Brain Institute. “This new way of thinking is what we have been waiting for. It’s a game changer.”
This work was supported by National Institutes of Health, Canadian Institutes of Health Research, Canada Foundation for Innovation, Michael J. Fox Foundation, Brain Canada, Ontario Brain Institute, Garfield Weston Foundation, Webster Foundation, Edmond J Safra Philanthropic Foundation, Parkinson Foundation, Parkinson Canada, the State of Arizona, Mayo Clinic, Banner Health, Fonds de Recherche du Quebec – Sante ́, Deutsche Forschungsgemeinschaft (German Research Foundation), German Federal Ministry of Education and Research, EU/EFPIA/Innovative Medicines Initiative, European Joint Programme on Rare Diseases, Niedersächsisches Ministerium für Wissenschaft und Kunst, Volkswagen Foundation, Petermax-Müller Foundation, German Parkinson Society, German Parkinson’s Disease Association, Parkinson Fonds Deutschland gGmbH, Damp Foundation and UHN Foundation.
Dr. Lang is a Professor in the Department of Medicine and the Jack Clark Chair for Parkinson’s Disease Research at the University of Toronto.
Höglinger GU, Adler CH, Berg D, Klein C, Outeiro TF, Poewe W, Postuma R, Stoessl AJ, Lang A E. A biological classification of Parkinson's disease: the SynNeurGe research diagnostic criteria. Lancet Neurol. 2024 Jan. doi: 10.1016/S1474-4422(23)00404-0.
The SynNeurGy model is based on a growing understanding that Parkinson's disease involves three key biological factors—a build-up of α-synuclein, neuron loss and the presence of specific gene variants—and that the relative contribution of each of these factors often differs between patients.