Effects of New Parkinson Disease Staging System on Clinical Trials and Future Research: Tanya Simuni, MD, FAAN
The head of the division of movement disorder at the Northwestern University Feinberg School of Medicine provided perspective on the impact of a newly published staging system that defines Parkinson disease by biologic features, not symptoms. [WATCH TIME: 4 minutes]
WATCH TIME: 4 minutes
"Variance is the biggest enemy of clinical trials. The tighter population you recruit, the better chance you have for an efficacious readout of your intervention."
Parkinson disease (PD) and dementia with Lewy bodies, 2 neurodegenerative conditions, are currently defined by their clinical features, with detection of α-synuclein pathology used as the gold standard to establish a definite diagnosis. Biomarker, clinical, epidemiological, and neuropathological data has shown that pathology of these conditions happens years before symptoms arise. This has led to potentially inappropriate cohorts of patients at various stages of their disease progression, making it only harder to truly understand the efficacy of tested drugs.
Recently, a published paper from patient, research, and industry leaders proposed a new definition for PD based on neuronal α-synuclein rather than clinical features. This staging system the neuronal α-synuclein disease integrated staging system (NSD-ISS), is rooted in the biological anchors of PD and the degree of functional impairment caused by clinical signs or symptoms. Comprised of 6 stages, stages 0-1 occur without signs or symptoms and are defined by the presence of pathogenic variants in the SCNA gene (stage 0), α-synuclein alone (stage 1A), or α-synuclein 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 nonmotor symptoms.
Led by Tanya Simuni, MD, FAAN, the proposed system is currently intended for research use only, with the goal to enhance trial design and improve drug development. Simuni, a professor of neurology and head of the division of movement disorder at the Northwestern University Feinberg School of Medicine, sat down with NeurologyLive® to discuss the long-term impacts this staging system has on the PD research community. She provided clarity on the purpose behind the paper, the role of α-synuclein in PD, and the next steps in expanding drug development.
