A technique that identifies the build-up of abnormal protein deposits linked to Parkinson’s disease in cerebrospinal fluid can accurately detect patients with the disease, according to research published in The Lancet Neurology. In addition, the findings suggest that the test can identify at-risk people and those with early, non-motor symptoms prior to diagnosis, which could in the future, support a framework for early detection and prevention of disabling motor symptoms, like tremors.
Researchers at Penn Medicine, along with the Parkinson’s Progression Markers Initiative (PPMI) and Michael J. Fox Foundation (MJFF), confirmed that the technique – known as α-synuclein seed amplification assay (αSyn-SAA) – is highly accurate at identifying Parkinson’s disease patients, and classifying them based on genetic and clinical markers.
“This research is a step forward for understanding the different pathologies of Parkinson’s disease,” said corresponding author Andrew Siderowf, MD, a professor of Neurology in the Perelman School of Medicine at the University of Pennsylvania and director of Penn’s Parkinson’s Disease and Movement Disorders Center. “The αSyn-SAA technique is a crucial tool to further our understanding of how Parkinson’s disease develops in patients with and without risk factors. Going forward, we will be able to use the test to connect patients with the most promising clinical trials based on their underlying biology. In the future, tests like αSyn-SAA could likely form the basis for personalized medicine for Parkinson’s disease.”
This technique amplifies very small amounts of misfolded aggregates of α-synuclein in samples from Parkinson’s patients to the point that they can be detected using standard laboratory methods. This approach builds on the ground-breaking discovery of synuclein protein deposits as a biological hallmark of Parkinson’s disease by researchers including Penn Medicine’s Virginia M.Y. Lee, PhD, the John H. Ware 3rd Professor in Alzheimer’s Research in Pathology and Laboratory Medicine, and the late John Q. Trojanowski, MD, PhD, a former professor of Geriatric Medicine and Gerontology in Pathology and Laboratory Medicine.
The Lancet Neurology paper outlines αSyn-SAA results from more than 1,100 participants from PPMI, including individuals with Parkinson’s disease, those with genetic or clinical risk factors but not yet diagnosed with Parkinson’s, and control volunteers. Samples of cerebrospinal fluid – which surrounds the brain and spinal cord – were analyzed using αSyn-SAA. The large-scale analysis confirms previous, smaller reports that αSyn-SAA gives positive results in 88 percent of all participants with Parkinson’s disease, including sporadic and genetic cases. Over 95 percent of control volunteers had negative test results.
In addition, a portion of participants had conditions that are known precursors to Parkinson’s disease, without a diagnosis. These conditions include rapid eye movement (REM) sleep behavior disorder, and unexplained loss of sense of smell. Among those recruited based on their loss of smell, 89 percent had positive αSyn-SAA results. Similarly, in REM sleep behavior disorder, positive αSyn-SAA results were present in 85 percent of cases. Results were also positive in some participants who carried genetic variants associated with Parkinson’s disease, but had no clinical manifestations of disease.
PPMI is an international study conducted at 33 academic centers in 12 countries. Penn’s Parkinson’s Disease and Movement Disorders Center has been a leading recruiting site for PPMI for over a decade. Penn’s effort is spearheaded by Nabila Dahodwala, MD, a professor of Neurology, and Charles Bae, MD, MHCI, an associate professor of Sleep Medicine and Neurology. Daniel Weintraub, MD, a professor of Psychiatry at Penn, also contributed to the publication.
“This is a very important milestone for Parkinson’s disease research,” Siderowf added. “Penn Medicine is proud to be one of the top recruiting sites for PPMI studies, bringing patients to clinical trials that will not only alter the course of their own disease, but move forward the science for detecting and treating the disease in future patients.”
This research was supported by PPMI. For more information on ongoing Parkinson’s disease research and clinical trials at Penn Medicine, visit https://www.med.upenn.edu/pdmdc/research-at-pd-and-mdc.html.