A ‘radically different’ way of looking at Parkinson’s disease

An international research team led by Krembil Brain Institute neurologist and senior scientist Dr. Anthony Lang has proposed a new model to classify Parkinson’s disease (PD).

Over the past few decades, researchers have discovered several biological factors that cause Parkinson’s disease. Key factors include an accumulation of the protein α-synuclein in the brain, which leads to neuron degeneration, and genetic factors that increase the risk of developing the disease. They also began to develop reliable methods for testing these factors, called biomarkers, in living patients.

Despite these advances, doctors continue to diagnose the disease based on clinical features, such as the presence of tremors and other common motor symptoms.

According to Dr. Lang, Lily Safra Chair in Movement Disorders at University Health Network (UHN) and Jack Clark Chair in Parkinson’s Research and professor in the Department of Medicine at the University of Toronto , this traditional approach to PD diagnosis does not take into account the complex biological processes involved.

“We know that Parkinson’s disease exists in the brain for one to two decades or more before clinical manifestations appear,” says Dr. Lang. “We therefore believe that current research should be guided by the biological determinants of the disease, rather than limited clinical descriptions of its signs and symptoms.”

He adds: “We need a radically different way of looking at this disease.”

In a recent article published in Neurology LancetDr. Lang’s team proposed a new biological model to classify Parkinson’s disease, called SynNeurGe (pronounced “synergy”).

The model emphasizes the important interactions between three biological factors that contribute to disease:

1. the presence of pathological α-synuclein in the brain (S);
2. signs of neurodegeneration, which occur as the disease progresses (N); And
3. the presence of genetic variants that cause or strongly predispose a person to the disease (G).

According to the team, this “NGS” classification system better accounts for the biological heterogeneity of Parkinson’s disease and the many ways in which this disease can present in patients. Therefore, the system could help researchers identify subgroups of patients with distinct disease processes and develop clinically meaningful disease-modifying therapies.

“We need to recognize that Parkinson’s disease can differ significantly from one patient to another. We are not dealing with just one disorder,” says Dr. Lang. “Our model provides a much broader and holistic view of disease and its causes.”

“With this new model, Dr. Lang is leading a truly pivotal international effort to redefine the biological complexity of Parkinson’s disease, which will lead to more advanced and streamlined research in this area and, ultimately, to precision medicine for patients,” said Dr. Lang. Jaideep Bains, co-director of the Krembil Brain Institute at UHN.

The team is confident that this new way of looking at Parkinson’s disease will help researchers study its molecular basis, distinguish it from other neurodegenerative diseases that share common biological characteristics, and identify targets for new treatments.

Despite these potential applications, Dr. Lang cautions that the model is intended for research purposes only and is not ready for immediate clinical application. Yet it is already raising 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 Movement Disorders Patient Advisory Committee at the Krembil Brain Institute of the ‘UHN, who currently lives with PD. “This new way of thinking is what we’ve been waiting for. It’s a game changer.”

“Without looking at the biology, it’s impossible to get answers. And without answers, we won’t have much-needed breakthroughs in Parkinson’s disease,” says Dr. Lang. “This new classification system and the future research project it will inspire is one of the most exciting things I have worked on in my career.”