Diagnostic and prognostic biomarkers for Parkinson's disease (U01)
Biomarkers that can detect Parkinson's disease (PD) pathology and that can detect disease progression will be incredibly helpful for patient care and proper clinical trial design. Successful identification of biomarkers of this disease will accelerate the discovery of a cure for PD. It is thought that inflammatory factors may play a role in the development of PD. As part of the NINDS Parkinson's Disease Biomarkers Program, this team will collect biological specimens from PD patients along with detailed clinical information including novel data on gait and balance. They will use blood samples collected from a large number of subjects with Parkinson's disease, as well as people who are healthy, and people with Alzheimer's Disease. In this way, they will be able to compare factors that are important for Parkinson's disease specifically, and not just generally applicable for people who are older, or for people with other types of neurological problems which would need different treatments. The biological specimens and the data collected by this team will foster collaboration across the entire Parkinson's Disease Biomarkers Program and create an important resource for the Parkinson's disease community, which is essential for advancement in the field.
This project seeks to discover a blood biomarker that changes in proportion to the severity of Parkinson disease (PD). Discovery of such a "biomarker" is important as this will greatly speed identification and testing of agents that may slow or halt the progression of PD, which is the major unmet need in this neurological disorder. This project consists of two separate parts: a clinical part which involves interacting with people with PD and a basic research part which involves analysis of blood samples looking for a biomarker. Dr. Dewey, who heads up the clinical portion of the project, will seek to identify and recruit 240 subjects with PD over a two-year period from whom we will collect blood and clinical information at baseline and at 6 month intervals for a minimum of 3 years. Cerebrospinal fluid (CSF) will be collected from 100 subjects who volunteer for this procedure using a spinal tap. Clinical information we plan to collect using various scales and surveys includes information on motor function, quality of life, mood, and activities of daily living. We will also be collecting computerized data on gait and balance using a new device recently acquired by UT Southwestern. Dr. German, who is in charge of the basic research component, will use serum from PD patients collected during Years 1-2 of the grant for comparison to serum samples from age/gender-matched normal controls and 50 age/gender matched Alzheimer's disease (AD) subjects from the Alzheimer's disease Center at UT Southwestern Medical School. These samples will be used in two projects: (1) We will determine whether the serum biomarkers for PD are useful for tracking disease progression. It is predicted that one or more of the PD-biomarkers will be elevated more in the serum of PD patients in Year-3 vs. Year 2 vs. Year-1. Next we will create a serum-based measure of PD severity, which will be utilized to predict progression over the 3-year period. (2) We will validate the serum biomarkers for PD with a new PD sample. We will use a new set of randomly selected PD serum samples, and normal control samples, to validate the utility of the PD biomarkers. Along with the PD samples will be an additional 20 subjects at a very early stage of the disease verified by a special SPECT scan. It is predicted that the PD biomarkers accurately identify PD cases, even when they are in the early stage of the disease.
Goals of Project
- Resource Building: Collect clinical data and new biological specimens from PD patients as a participant in the NINDS Parkinson's Disease Biomarkers Program (PDBP). We will collect clinical data and new biological specimens from PD patients as a participant in the NINDS PDBP. We will acquire 120 subjects with PD over a two-year period from the Clinical Center for Movement Disorders at UT Southwestern Medical Center. We will collect blood (serum and plasma) along with clinical information at baseline and at 6 month intervals for a minimum of 3 years. CSF will be collected from 100 subjects. All samples will be submitted to the NINDS Biorepository and Data Management Resource in accordance with NINDS PDBP policies.
- Discovery: Identify serum biomarkers for PD. We will also apply serum samples to two biomarker discovery platforms : 1) a peptoid library and 2) the Myriad - Rules Based Medicine (RBM) DiscoveryMAP 1.0 multiplex platform, to develop a PD protein-based diagnostic profile using random forest analyses.
- Discovery: Determine whether the serum biomarkers for PD are useful for tracking disease progression. We will determine how accurately both the peptoid and protein biomarkers track disease progression over a 3 year period.
- Replication: Replicate the serum biomarkers for PD with a new PD sample. We will use a new set of randomly selected PD serum samples (n=80), and normal control samples (n=100) to validate the utility of the PD biomarkers identified using the peptoid and RBM approaches.
- 120 Parkinson's disease participants (varying stages of disease)
- 58 Healthy participants (various ages)
Congratulations, to the University of Texas Southwestern for enrolling 238 participants into their PDBP project as of October 9, 2015 and completing, through the PDBP Data Management Resource, electronic documentation for 215 baseline visits and 218 six month visits, 180 twelve mits!
Presentation from the NINDS PDBP Kick-off Meeting in November 2012: Dewey and German Project Kickoff Presentation