A paper published in The Lancet Neurology journal by leaders of the Parkinson’s Progression Markers Initiative (PPMI), a Parkinson’s biomarker study sponsored by The Michael J. Fox Foundation for Parkinson’s Research (MJFF), confirmed a significant breakthrough in the search for a Parkinson’s biomarker: a biological test for Parkinson’s disease that demonstrates high diagnostic accuracy, differentiates molecular subtypes, and detects disease in individuals before cardinal movement symptoms arise.
The new test, known as the alpha-synuclein seed amplification assay (αSyn-SAA), aims to herald the revolutionary ability for research to define Parkinson’s disease biologically, offering a critical tool for clinical trial design and assessment of treatment effects, and for early detection of disease pathology.
As authors from PPMI detail in The Lancet Neurology, the test detects synuclein pathology, one of the two biological hallmarks of Parkinson’s disease (alongside dopaminergic transport dysfunction, which can be visualized using DaTScan).
As a result, researchers and clinicians can use biology (vs. clinical assessments and patient-reported outcomes) to identify, define and monitor Parkinson’s objectively, based on cellular pathology in the living body.
“Validation of this biomarker launches a new, biological era in Parkinson’s research,” says Kenneth Marek, MD, PPMI Principal Investigator and president and senior scientist at the Institute for Neurodegenerative Disorders. “Using αSyn-SAA, we are already unlocking new understanding of Parkinson’s, which will transform every aspect of drug development and ultimately clinical care. We will rapidly be in a position to test new therapies in the right populations, target the right therapy to the right patient at the right time, and launch studies of agents with potential to prevent Parkinson’s disease altogether. This is what PPMI was built to do, and we are especially grateful to the thousands of study participants whose contributions have enabled this watershed moment.”
The paper, co-led by Andrew Siderowf, MD, PPMI Investigator and Director, Parkinson Disease and Movement Disorders Center at the University of Pennsylvania and Luis Concha, PhD, Director, Research and Development at Amprion, outlines αSyn-SAA results from more than 1,100 PPMI participants including individuals with Parkinson’s disease, those with genetic and/or clinical risk factors but not diagnosed with Parkinson’s, and control volunteers.
The large-scale analysis in PPMI confirms previous reports—including from MJFF-funded work—that αSyn-SAA can distinguish Parkinson’s from control volunteers with a robust sensitivity of 88% and specificity of 96%.
As an objective and reliable biomarker of Parkinson’s biology, αSyn-SAA will significantly decrease the risk for industry to invest in the development of potential blockbuster therapies, including preventive agents, and increase the speed and efficiency with which these therapies can be developed, tested, and brought to market.
With αSyn-SAA, it will be possible to establish objective endpoints for clinical trials of Parkinson’s treatments, ensure study participants exhibit appropriate pathology, and detect therapy-induced changes in their status, according to The Michael J. Fox Foundation for Parkinson’s Research.