New Staging System for Parkinson Disease and Dementia with Lewy Bodies Based on Biologic Factors Proposed

A position paper published in The Lancet Neurology proposes a new research framework for staging and defining Parkinson disease (PD) and dementia with Lewy bodies (DLB) according to biological factors as well as clinical symptoms. The proposed neuronal α-synuclein disease integrated staging system (NSD-ISS) is intended to facilitate interventional research trials at early disease stages and constitutes the first system for biological definition and staging for PD and DLB.

The NSD-ISS framework was developed through a process of multistakeholder collaboration initiated by an international working group, which hosted a discussion including people with PD and their families, leaders in the field of neurology and neuroscience, and stakeholders from industry and governmental organizations. The process also invited public comment and in total included over 500 stakeholders from around the world.

Staging on the NSD-ISS is based on the presence of cerebrospinal fluid (CSF) neuronal α-synuclein (asyn), as detected by the α-synuclein seed amplification assay (αSyn-SAA); dopaminergic neuronal dysfunction associated with disease progression, as detected by dopamine transporter (DaT) scan; and clinically assessed functional impairment. The system unifies PD and DLB along a single continuum of disease progression. Stage 0 occurs without signs or symptoms of disease, defined only by pathogenic variants of the SNCA gene.

• Stage 1 occurs without signs or symptoms of disease and is defined by either the presence of asyn alone (stage 1A) or the presence of asyn and dopamine dysfunction (stage 1B).
• Stage 2 occurs with clinical manifestation of disease, defined by subtle signs and symptoms without functional impairment.
• Stages 2B through 6 occur with clinical manifestation of disease, the presence of both asyn and dopamine dysfunction, and stage-specific increases in functional impairment.

“This new research framework promises to transform clinical trial design as we know it,” said Diane Stephenson, PhD, paper coauthor and Executive Director of the Critical Path for Parkinson's Consortium at Critical Path Institute. “This is how the field will meaningfully and tangibly achieve smarter and faster drug trials and treatments that can slow or halt disease progression, and perhaps one day, prevent the disease process from occurring altogether.”

At present, the NSD-ISS is intended to be used for research purposes only.