Protein Levels in Spinal Fluid Correlate to Posture and Gait Difficulty in Parkinson's Disease
- Study sponsored by The Michael J. Fox Foundation for Parkinson's Research found lower alpha-synuclein levels in spinal fluid associated with postural instability/gait difficulty phenotype.
- Beta-amyloid levels correlated with cognitive recall scores.
- These findings may point to symptom-specific biomarkers useful for pathological investigation and study subject stratification.
NEW YORK (December 19, 2017) -- The Fox Investigation for New Discovery of Biomarkers (BioFIND) -- a cross-sectional, observational study sponsored by The Michael J. Fox Foundation for Parkinson's Research (MJFF) -- has profiled Parkinson's-associated protein levels and correlation to clinical experience in findings published online in Movement Disorders earlier this month. This analysis points to associations that could inform subject selection for clinical trials, speeding testing of symptomatic and disease-modifying therapies.
"This report is an important contribution in our efforts to understand and quantify Parkinson's biology to accelerate drug development," said MJFF Senior Vice President of Research Programs Mark Frasier, PhD, an author on the paper. "BioFIND is a partnership between our Foundation, academia, government and -- most importantly -- research volunteers to measure this disease and the impact of new treatments."
BioFIND is supported in part by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, and led by principal investigator Un Jung Kang, MD, chief of the Division of Movement Disorders at Columbia University. The study collected data and samples from 120 people with moderately advanced Parkinson's disease and 100 control volunteers across eight academic sites in the United States at two points over two weeks.
Study investigators report levels of the protein alpha-synuclein were lower in cerebrospinal fluid among participants with postural instability/gait difficulty phenotype. Levels of beta-amyloid protein -- which accumulates into plaques in Alzheimer's disease -- were lower in the Parkinson's cohort and correlated to scores on a cognitive recall test (Montreal Cognitive Assessment).
"These associations between protein levels and clinical symptoms can help us select participants for clinical trials. For example, people with lower beta-amyloid may be more likely to develop memory problems and therefore would benefit more from a cognitive therapy. Enrolling this population in trials can help us see a treatment effect more clearly than testing the therapy on people who will not have this symptom," said lead author Jennifer G. Goldman, MD, MS, associate professor at Rush University Medical Center in Chicago.
The study also showed alpha-synuclein levels in plasma and saliva did not differ between people with Parkinson's and control volunteers, and alpha-synuclein did not significantly correlate among biofluids. These are important insights for the ongoing pursuit of accessible biomarker tests to diagnose and track the disease.
Next steps include validation of these findings in the MJFF-sponsored biomarkers study, the Parkinson's Progression Markers Initiative (PPMI), which is following more than 1,500 people with Parkinson's or risk factors and control volunteers over at least five years. Additionally, trials ongoing or launching in the near future could use alpha-synuclein or beta-amyloid levels as exploratory biomarkers in motor symptom or cognition drug trials, respectively.
BioFIND and PPMI make de-identified data and biospecimens available to qualified researchers for additional discovery and validation work toward scientific breakthroughs (read more at michaeljfox.org/dataspecimens).
About The Michael J. Fox Foundation for Parkinson's Research
As the world's largest nonprofit funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $750 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world.