Next Steps in Bringing PD Staging System to Clinic: Tanya Simunui, MD


The head of the division of movement disorder at the Northwestern University Feinberg School of Medicine discussed the steps necessary in bringing a newly established Parkinson disease defining system to clinical settings. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

"In the future, we need to apply a number of things from the staging [system] to a large cohort of individuals. To do that, we need those individuals to be biologically characterized. We need them to have synuclein biomarker, we need them to have a dopaminergic dysfunction. That is essentially important."

For years, clinicians defined patients with Parkinson disease (PD) based on clinical characteristics and symptoms. A recently published report proposed that, given biomarker advances in enabling accurate detection of pathological α-synuclein in cerebrospinal fluid using a seed amplification assay, it was time to redefine PD and dementia with Lewy bodies as neuronal α-synuclein disease rather than as clinical syndromes. The newly proposed biological definition establishes a staging system, the neuronal α-synuclein integrated staging system (NSD-ISS), that is rooted in the biological anchors and the degree of functional impairment caused by clinical signs or symptoms.

The NSD-ISS integrates 2 core biomarkers: aggregated αsyn and dopamine dysfunction. The staging system starts with stages 0-1, which occur without symptoms and are defined by the presence of pathogenic variants in the SCNA gene (stage 0), α-synuclein alone (stage 1A), or αsynuclein and dopaminergic dysfunction (stage 1B). Stages 1 and 2 are based on objective biomarkers, while stages 3-6 require these biomarkers and progressive motor and other nonmotor symptoms. Although the NSD-ISS stages are sequential, differences in rate of progression might limit practical observation of early stages or sequential progression through subsequent stages in some individuals.

Lead investigator Tanya Simuni, MD, head of the division of movement disorder at the Northwestern University Feinberg School of Medicine, stressed that this staging system is intended for research purposes, for now. In an interview with NeurologyLive®, she provided thoughts on how this type of approach can change clinical care and the steps needed to take before integrating it. She spoke specifically on the resources needed to fully characterize patients, when its appropriate to test for disease biology, and what to do for individuals who have a mixed pathology of PD and dementia with Lewy bodies.

1. Simuni T, Chahine LM, Poston K, et al. A biological definition of neuronal a-synuclein disease: towards an integrated staging system for research. Lancet Neurol. 2024;23(2):178-190. doi:10.1016/S1474-4422(23)00405-2.
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