A “landmark” paper published in The Lancet Neurology by leaders of the Parkinson’s Progression Markers Initiative (PPMI)—a study sponsored by The Michael J Fox Foundation (MJFF) for Parkinson’s Research—confirms what the charity describes as “the most significant breakthrough yet” in the search for a Parkinson’s disease biomarker: a biological test 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), heralds 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 per an MJFF press release.
As PPMI authors 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 visualised using DaTScan. According to the MJFF, as a result, and for the first time since James Parkinson first characterised the disorder in 1817, researchers and clinicians can use biology (versus 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,” said Kenneth Marek, PPMI principal investigator, and president and senior scientist at the Institute for Neurodegenerative Disorders (Yale University, New Haven, USA). “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 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 that αSyn-SAA can distinguish Parkinson’s from control volunteers with a “stunningly robust” sensitivity of 88% and specificity of 96%, the MJFF release adds. Today, the study has enrolled nearly 2,000 participants and is actively enrolling Parkinson’s patients, at-risk individuals and control volunteers at 51 clinical sites globally.
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, according to the MJFF.
“There are many ways I am involved with the work of the foundation, but I come to this result first and foremost as a Parkinson’s patient,” said Michael J Fox. “I am deeply moved by this breakthrough and endlessly grateful to the researchers, study participants and funders who have endeavoured to bring us this far. When we started PPMI, we were not casting about for fish—we were going after a whale. Now, here we are. Together, we are making a cure for Parkinson’s inevitable.”