An MJFF-directed team has published recommendations on how to measure the key Parkinson's protein alpha-synuclein in blood and spinal fluid. This "user manual" can lead to more accurate and replicable results, helping us better understand and develop treatments for Parkinson's disease (PD).
Clumps of alpha-synuclein are the hallmark of Parkinson's, and scientists want to develop a way to measure this protein to diagnose or monitor PD. Such measures are called biomarkers.
"There are no definitive biomarkers to diagnose PD, determine who might develop PD or predict disease course. Biomarkers are also crucial in clinical trials to show if a drug is 'working,'" says Samantha Hutten, PhD, MJFF senior associate director of research programs. "Given the number of disease-modifying treatments in clinical testing, lab tests to reproducibly and reliably measure alpha-synuclein have never been more important."
Controlling What We Can for Best Test Results
While there are alpha-synuclein tests available, results can vary from study to study and even from the same person at different times.
"There are biological reasons and technical reasons for variability. These tests are still run by human beings and handling samples leads to different outcomes," says Brit Mollenhauer, MD, assistant professor at University Medical Center Goettingen in Germany and lead author of the recommendations paper, published in the August issue of the journal Movement Disorders.
The biological factors -- such as a person's genetics -- we cannot control, but others we can. Much like how cold versus warm butter or a glass versus metal pan can make a difference in a dessert, temperature, equipment and other situational factors influence alpha-synuclein tests.
The new paper recommends standard procedures from collecting spinal fluid in the morning with a fasting patient to strategies for checking for contamination to what tubes to use to store the sample. Controlling for these factors can remove some confounders that may influence results, giving greatest chance of accuracy and replication.
"Our hope is by sharing these guidelines with the research community, biomarker research and drug trials will accelerate as investigators are able to build on the knowledge, insight and previous experience of the field," says Dr. Hutten.
Assembling an Expert Team for Rigorous Replicable Research
This work is part of our MJFF Investigating Synuclein Consortium, a group of 30 academic and industry investigators around the world who are developing alpha-synuclein tests with funding from the Foundation. These investigators share data, critical information and tools as they work toward the same goals.
For this project, scientists compared available alpha-synuclein tests on the same set of samples (spinal fluid, blood and saliva).
"This parallel approach with the same samples gave us confidence in our recommendations and let us come to conclusions more quickly," says Dr. Mollenhauer. "The Michael J. Fox Foundation is uniquely positioned to organize such a program."
The authors are quick to say their work is not done yet. They will continue investigating variability and update their recommendations as technology and knowledge advances.
The consortium also is working to define and assess measures of other types of alpha-synuclein. This project looked at tests of total alpha-synuclein; other types or species of the protein have been linked to PD.