Paradigm Shift in Neurological Diseases

The challenge in developing effective treatments for Parkinson's disease lies in the complexity of this condition. Some forms have a genetic origin, while others are linked to environmental factors, with patients exhibiting a wide range of symptom severity. Moreover, the diagnosis of Parkinson's is currently made very late, when the disease has already been present in the brain for a decade or more.


In an article published in The Lancet Neurology, a group of scientists argues that this complexity demands a new method of classifying the disease for research purposes. This classification is not based on clinical diagnosis but on biology, and the authors have named their biological model "SynNeurGe".

"Syn" refers to alpha-synuclein, a protein that, in most Parkinson's patients, causes abnormal deposits known as "Lewy bodies." The anomalies in synuclein, which characterize the disease, likely cause degenerative changes in the brain and affect movement, thought, behavior, and mood.

"Neur" represents neurodegeneration and describes the degradation of neuronal brain function. In medical practices, certain specific neurons of the dopaminergic system are used to diagnose Parkinson's disease. However, in the "SynNeurGe" model, neurodegeneration of all brain areas is included in the classification.

"Ge" symbolizes genetics, which plays a complex role in Parkinson's disease. It has been discovered that mutations in many different genes predispose individuals to this condition. The likelihood of developing the disease therefore depends on three factors: the gene involved, the specific mutation within that gene, and environmental exposures.

The authors believe that for research purposes, patients should be classified based on the presence or absence of these three factors. This would make it possible to identify affected individuals before symptoms appear, facilitating the development of treatments tailored to the unique biology of these patients. Currently, a diagnosis is made based on their symptoms and signs, even though the disease has been present in their brains for years. Changing the classification criteria will enable researchers to detect the disease earlier (before symptoms occur) and target specific patient groups with common biological characteristics, thereby increasing the likelihood of developing effective drugs.

"So far, it's only research work, but it represents a major shift in thinking," says one of the study's authors, Dr. Ron Postuma, a clinical researcher at The Neuro (Montreal Neurological Institute-Hospital) of McGill University. "Upon reflection, it's odd that we have to wait for Parkinson's patients to experience significant symptoms to make a diagnosis. We don't wait for a person to suffer before diagnosing cancer, because, with luck, it is detected and screened before symptoms manifest. Thus, this research-derived classification is an essential step in our thinking about Parkinson's disease in the 21st century."

"A Biological Classification of Parkinson's Disease: The SynNeurGe Research Diagnostic Criteria" was published by Günter U. Höglinger et al., in the journal The Lancet Neurology on January 22, 2024. The lead author, Dr. Anthony Lang, holds the Lily Safra Chair in Movement Disorders at the Krembil Brain Institute of the UHN, holds the Jack Clark Chair for Parkinson's Disease Research, and is a professor in the Department of Medicine at the University of Toronto.