Background and Rationale
Given the growing consensus around alpha-synuclein and DJ-1 as likely biomarkers for Parkinson’s Disease, the PPMI planning committee designed and completed a 24-hour verification study in controls to determine whether biomarkers are changed within the course of a day. The results prompted the committee to see value in conducting a similar study in PD subjects to determine whether the findings in younger controls were consistent across the PD subjects and elderly controls. The objectives for both studies are three-fold:
- Determine diurnal fluctuations of DJ-1 and alpha-synuclein in CSF of PD and control individuals
- Determine within-subject variability and between subject variability
- Establish a bank of biosamples (CSF and blood) that can be utilized for assay development and future biomarker validation
Qualification Study in Controls
Study Design
The protocol included the collection of CSF and serum/plasma at 11 time points within a 26 hour time period. This exact protocol was repeated two weeks later in all subjects. The study recruited 13 control volunteers (30-55 years old), of whom 9 were male and 4 were female. The study was completed in Fall 2010.
Click here to review the protocol for the Qualification Study in Controls.
Analyses
The samples collected were analyzed for DJ-1, alpha-synuclein, and hemoglobin levels. Assays with the following characteristics were tested:
- Alpha-synuclein ELISA: Dynamic range: 4-2000pg/mL; DJ-1 Assay: R&D Biosystems ELISA kit
- Hemoglobin detection: Bethyl laboratories commercial ELISA kit
The study determined that there was a change in the biomarkers over the course of 24 hours, which suggests that the time at which CSF samples are collected in clinical trials could affect the standardization of the study. The complete results of these analyses will be posted to this site soon.
Samples from the PPMI Qualification Study in controls are available to the scientific community for research projects. For more information about accessing these samples, Contact Us.
Qualification Study in PD Subjects
Study Design
A similar study to the Qualification Study in Controls is now being repeated in Parkinson’s patients and elderly controls to determine whether the same changes in proteins over the course of a day occurs in a different population. The study will recruit 12 PD patients and 6 age- and gender-matched controls who will be hospitalized for 4 days. Two days will require lumbar catheterization, which will be followed by a day of rest and monitoring.
Click here to view the protocol for the Qualification Study in PD Subjects.
Analyses
The following assays will be performed on the samples collected in the Qualification Study in PD Subjects:
- Alpha-synuclein ELISA: Dynamic range: 4-2000pg/mL; DJ-1 Assay: R&D Biosystems ELISA kit
- Hemoglobin detection: Bethyl laboratories commercial ELISA kit
