November 2024

NEUROSCIENCES

IMPROVING DIAGNOSIS AND TRACKING OF NEURODEGENERATIVE DISEASES

Featuring: Tanya Simuni, MD
Investigators led by Tanya Simuni, MD, the Arthur C. Nielsen, Jr., Research Professor of Parkinson’s Disease and Movement Disorders, have defined new biologic and clinical biomarkers for better identifying patients with different stages of Parkinson’s disease and Lewy body dementia, according to a recent study published in NPJ Parkinson’s Disease.  

“Currently, the field has been using clinically defined diagnostic criteria of Parkinson’s disease or dementia with Lewy bodies and there are no established frameworks of biological and clinical subtyping,” said Simuni, who is also chief of Movement Disorders in the Ken and Ruth Davee Department of Neurology and director of the Parkinson’s Disease and Movement Disorders Center.  

“The major significance of this paper is it provides the anchors, it provides the framework to validate what we’ve demonstrated to build on longitudinal data and to apply the same framework to the preclinical stages of the disease,” Simuni said.  

​Neuronal alpha-synuclein disease (NSD) defines a neurodegenerative disorder that manifests when abnormal amounts of alpha-synuclein protein build up in neurons (Lewy bodies) and other parts of the brain which can lead to Parkinson’s disease or Lewy body dementia.  

Until recently, there was no framework to define either disease prior to symptom onset. Previous work led by Simuni and published in Lancet Neurology had recently established the neuronal alpha-synuclein disease integrated staging system (NSD-ISS) to identify individuals with Lewy body pathology. 

In the current study, Simuni’s team aimed to develop and apply biologic and clinical data-informed definitions for the NSD-ISS across disease stages.   

Participant data from three independent studies were evaluated: the Parkinson’s Progression Markers Initiative (PPMI), the PASADENA study and the SPARK study. Patients enrolled as having Parkinson’s disease, prodromal (early-stage) disease, or healthy controls were defined and staged based on biological, clinical and functional biomarkers (“anchors”) at baseline. 
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“We first reviewed the landscape of what clinical measures are available in the field that have been applied in majority of the recently completed or conducted studies, and programmatically put together data-informed anchors and then applied those anchors to the PPMI, PASADENA and SPARK cohorts,” Simuni said.  

​Across the three studies, a total of 1,741 participants had data from alpha-synuclein seed amplification assays, which detect abnormal proteins levels. Of these participants, approximately 60 percent were alpha-synuclein positive and consistent with NSD. 

Among patients with sporadic Parkinson’s disease, 93 percent had NSD. The distribution for Stages 2B, 3, and 4 disease across these patients was 25 percent, 63 percent, and 9 percent, respectively. The average time to develop a clinically meaningful outcome was 8.3, 5.9, and 2.4 years for baseline stage 2B, 3, and 4.  

The results more effectively define the baseline heterogeneity of individuals currently defined as having early Parkinson’s disease, according to Simuni, and additional research on the validation of these anchors in longitudinal studies is needed.  

“Our data strongly support the concept of the biological definition and staging framework both to optimize a study population prior to symptoms and to identify a study population with more homogenous functional impairment and disease progression at the start of symptoms. The conceptual framework and operational definitions provide an opportunity to build on the current NSD-ISS framework to further inform therapeutic development,” the authors wrote.  

​“This was a concerted effort of academicians, people in industry because they need this framework to develop therapeutics in early stages of the disease, regulators, preclinical scientists, advocacy organizations and, very importantly, people with lived experiences,” Simuni added. “This is truly a multi-stakeholder effort.”  

Funding support for the data analysis was provided by The Michael J. Fox Foundation for Parkinson’s Research which also is the sponsor of the PPMI study, the largest observational study in Parkinson’s disease aiming to develop biomarkers to accelerate therapeutic development in Parkinson’s disease and related disorders.  
​This article was originally published in the Feinberg School of Medicine News Center on November 22, 2024. ​
Tanya Simuni, MD, the Arthur C. Nielsen, Jr., Research Professor of Parkinson’s Disease and Movement Disorders and chief of Movement Disorders in the Ken and Ruth Davee Department of Neurology, was senior author of the study published in NPJ Parkinson’s Disease. 

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