Last month the 1,000th subject was enrolled in the Parkinson’s Disease Biomarkers Program (PDBP), marking a major milestone in the efforts of NINDS to develop a method to predict the early onset—and track the progression—of this debilitating neurological disorder.
We have made considerable progress in developing treatments, but people with Parkinson’s still suffer. While current treatments are most effective at alleviating early symptoms of the disease, symptoms in later stages are less responsive, and no intervention has been found to slow disease progression or prevent it. Like many neurological diseases, the search for better Parkinson’s treatments has been hindered by the fact that symptoms—including uncontrollable shaking, rigidity, and impaired balance—only start appearing well after the disease has begun to cause significant changes in the brain.
Currently, we cannot identify the biological signature of the disease—the accumulation of aggregates of a protein called synuclein (so-called Lewy bodies) inside neurons and the loss of neurons in specific regions of the brainstem—in living people. Finding biological signatures in blood or other body tissues or fluids that can be detected in patients would allow us to track the progression of disease, and, importantly, give us a way to quantify the effectiveness of potential therapies over the course of treatment. Ideally a biomarker would enable screening for the presymptomatic stage of the disease, and subsequent testing of therapies that delay or prevent disability from ever occurring. Such signatures, or biomarkers, may take the form of proteins or other molecules created by the body; a good example is cholesterol, which is often used as a biomarker linked to heart disease, or high blood levels of glucose, which serves as a biomarker for diabetes. The exciting advances in PET scan tracers to label protein aggregates in the brain of living persons with Alzheimer’s disease may also blaze a path toward similarly useful tracers to label aggregates of synuclein in persons with Parkinson’s disease.
Since symptoms get worse over time, developing biomarkers for Parkinson’s could lead to earlier diagnosis and help spur the development of treatments to slow progression of the effects of Parkinson’s. The ultimate hope is that by combining biomarker signatures with drug discovery efforts, the Parkinson’s research community will uncover a cure for the more than one million people in the United States afflicted with the disease. So far, several candidate biomarkers for Parkinson’s have been proposed, but to date none has been proven to predict disease onset or progression reliably.
Launched in January 2013, the NINDS Parkinson’s Disease Biomarkers Program (PDBP) aims to accelerate the search for biomarkers through eleven research projects. Seven of the research sites also collect clinical samples using a standardized methodology for the collection of blood, DNA, and cerebral spinal fluid (CSF). These biological samples are stored at the NINDS Repository; scans of subjects’ brains taken with PET and MRI imaging, and clinical information such as medications and neurological exam results, are also collected and shared online among PDBP researchers via a web-based bioinformatics tool called the Data Management Resource (DMR). This state-of-the-art tool received the 2014 Best Overall Excellence.Gov Award in recognition of the best government information technology system.
The PDBP DMR accelerates the search for biomarkers by streamlining the sharing of the collected patient data with the entire community of Parkinson’s disease researchers, even those who are not part of the program. In addition, researchers can use the DMR tool to request that biological samples be shipped from the NINDS Repository to their labs for further study. We anticipate that this resource will become a launching pad for a variety of additional projects exploring multiple approaches to developing treatments for neurological diseases. As such, we strongly encourage any and all researchers working on Parkinson’s to utilize this incredible resource.
The eleven PDBP research groups (see bottom of post for brief project descriptions) are using the program’s aggregated data to test existing candidate biomarkers, discover new candidate biomarkers, and develop tools to streamline the collection and analysis of samples collected from patients. Additional research groups will join the program in the coming year.
In just over 18 months, the program has recruited more than 1,000 subjects (see infographic), around 600 with a diagnosis of Parkinson’s and 400 age-matched controls. To date, approximately 1,500 biological samples and 380 MRIs have been collected. By the end of the five-year program 1,500 subjects—900 with Parkinson’s and 600 controls—are expected to be enrolled, with each individual contributing clinical data and biological samples at least twice a year. Given that these numbers are well ahead of schedule, this project has so far been a remarkable accomplishment. The real measure of success for the program, however, will be how many researchers make use of this wonderful resource and what advances emerge from their studies.
This NINDS biomarker project complements previously established efforts supported by the Michael J. Fox Foundation (MJFF), which is sponsoring two biomarker projects of its own. The MJFF Parkinson’s Progression Marker Initiative (PPMI) has enrolled 800 individuals since it began in 2010, while the Fox Investigation For New Discovery of Biomarkers (BioFIND) launched in 2012 with the goal of collecting biological samples from 120 Parkinson’s patients and 120 age-matched controls. Working together, NINDS and MJFF have assembled powerful teams of patients, investigators and resources to attack this scientific problem.
I very much appreciate the contribution of each and every individual who has participated, and continues to participate, in the biomarker program. The time and energy these folks have devoted are critical to the program’s success. Take, for example, Dr. Paul Zimmet, the first subject enrolled in the study. Paul was a dentist with his own practice when he was diagnosed with Parkinson’s seven years ago. Soon after his diagnosis, Paul enrolled in his first Parkinson’s study and has to date been part of a dozen different studies to help researchers improve diagnosis and find better treatments. Please watch the video above to learn more about the biomarker program and hear more about why Paul enrolled and his experience in the study.
For more information about the program, please visit:
NINDS Parkinson’s Disease Biomarkers Program Infographic (PDF)
Video of a subject describing his experience in Parkinson’s Disease Biomarkers Program
Brief Description of PDBP projects:
Roy Alcalay, Ph.D., Columbia University, New York
Given the variability in symptoms and prognoses across Parkinson’s patients, many researchers theorize that there are several subtypes of the disease. Dr. Alcalay’s group is searching for genetic markers that can identify individuals with various subtypes.
F. Dubois Bowman, Ph.D., Columbia University, New York
This group is developing statistical tools to analyze data from brain imaging, genetic, molecular and clinical tests, in order to discover biomarkers which, in combination, can better predict the course of Parkinson’s disease than a single biomarker might be able to do.
Alice Chen-Plotkin, M.D., University of Pennsylvania, Philadelphia
This team seeks to confirm several candidate biomarkers they have identified, and search for others by using a novel, broad-ranging approach to measure the levels of more than 400 proteins in blood.
Ted Dawson, M.D., Ph.D., Johns Hopkins University, Baltimore
This team seeks to gain a clearer picture of the early clinical features of Parkinson’s – including changes in cognition and sleep – and to correlate those changes with potential biomarkers in blood and CSF.
Dwight German, Ph.D., and Richard Dewey, Ph.D., University of Texas Southwestern Medical Center at Dallas
Based on evidence that immune responses play a role in Parkinson’s, the researchers will investigate whether disease progression is related to changing levels of antibodies and other proteins in blood and CSF.
Xuemei Huang, M.D., Ph.D., Pennsylvania State University, University Park
This team will seek to determine whether state-of-the-art magnetic resonance imaging (MRI) scans can reveal subtle structural and chemical changes in the brain, including iron accumulation, during Parkinson’s.
Vladislav Petyuk, Ph.D., Battelle Pacific Northwest Laboratories, Richland,Washington
This group will seek to identify new components of the Lewy bodies that accumulate in the brain during Parkinson’s, and then use ultra-sensitive methods to see if any of these proteins have leaked into CSF or blood.
Clemens Scherzer, M.D., Brigham and Women’s Hospital, and Harvard University, Boston
This team will investigate whether Parkinson’s is associated with changes in the activity of non-coding, “dark matter” genes (which do not make proteins) in brain tissue, blood and CSF. The team also will integrate the PDBP with a Parkinson’s biomarkers study at the Harvard Neurodiscovery Center, which has already enrolled about 2,000 individuals.
Andrew West, Ph.D., University of Alabama at Birmingham
This team discovered that the Parkinson’s-related protein LRRK2 and many other proteins can be detected in urine, within microscopic structures called exosomes; they will investigate whether exosome-related proteins can serve as biomarkers.
David Vaillancourt, Ph.D., University of Florida, Gainsville
Dr. Vaillancourt and his team are using non-invasive imaging techniques that enable them to take snapshots of an individual’s brain at different stages of disease. These snapshots not only enable them to look at changes in the appearance of the brain, but also in how the brain is functioning and interacting with its various anatomical regions associated with movement and cognition.
Jing Zhang, M.D., Ph.D., University of Washington, Seattle
CSF appears to contain potential biomarkers, but blood is easier to obtain. Therefore, this group’s strategy is to conduct an expanded search for biomarkers in CSF and then search again for the strongest candidates in blood.