A neurologic disease paradigm shift

One of the things that makes developing effective treatments for Parkinson disease so challenging is its complexity. While some forms are caused by genetics, others have environmental factors, and patients can show a wide range of symptoms of varying severity. Diagnosis of Parkinson disease is also currently made very late, after the disease may have been in the brain for a decade or more.

In a paper published in The Lancet Neurology, a group of scientists argue that this complexity demands a new way of classifying the disease for research purposes, one based not on clinical diagnosis but biology. The authors have called their biological model “SynNeurGe”.

The “Syn” stands for alpha-synuclein, a protein that in most patients with Parkinson disease causes abnormal deposits called Lewy bodies. Abnormalities in synuclein identify and probably cause degenerative changes in the brain that can impact movement, thinking, behavior and mood.

“Neur” stands for neurodegeneration. This is the breakdown of the function of neurons in the brain. In doctor’s offices, specific neurons in the dopamine system are the way that Parkinson disease is diagnosed. In the SynNeurGe model, however, neurodegeneration in all areas of the brain is included in the classification.

The “Ge” stands for genetics. The role of genetics in Parkinson disease is complex. Mutations in many different genes have been found to predispose someone to the disease. The likelihood of developing Parkinson disease depends on the gene involved, the specific mutation within the gene and environmental exposures.

The authors argue that for research purposes, patients should be classified by the presence or absence of these three factors. This would allow the identification of patients with Parkinson disease before symptoms appear and aid the development of treatments tailored to patients’ unique biology. Right now, patients are diagnosed based on symptoms and signs, even though the disease may have been present in their brain for many years . By shifting classification criteria, researchers can identify disease earlier (even before people may experience symptoms), and target specific patient groups that have more in common with each other biologically, giving drug development a higher chance of success.

“Although this is still for research purposes, this is a major shift in thinking,” says Dr. Ron Postuma, a clinician-scientist at The Neuro (Montreal Neurological Institute-Hospital) of McGill University and one of the study’s authors. “If you think of it, it’s quite unusual that we’ve had to wait until Parkinson’s patients have important symptoms before we could make a diagnosis. We don’t wait for someone to feel pain from cancer before we diagnose it. Instead, we detect and diagnose it, hopefully before someone is aware of any symptoms. This research classification is a critical step towards bringing our thinking about Parkinson’s into 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 Lancet Neurology on Jan. 22, 2024, senior author Dr. Anthony Lang, the Lily Safra Chair in Movement Disorders at UHN’s Krembil Brain Institute, and the Jack Clark Chair for Parkinson's Disease Research and a Professor in the Department of Medicine, at the University of Toronto.

Source: News Release
McGill University
January 23, 2024