Objective/Rationale:
We aim to assess miRNA stability and evaluate the potential of previously identified PD-predictive circulating miRNAs as progression biomarkers for PD using MJFF DATATOP biospecimens.
Project Description:
First, miRNA integrity of the DATATOP samples (placebo group, early and untreated PD) will be evaluated to ensure the “viability” of miRNAs for biomarker study. Next, baseline (year 0) and endpoint visit (year 1–2) serum of 30 subjects from the same group of PD patients will be used to evaluate any miRNA expression changes within 1-2 years using previously-identified PD-predictive biomarkers and quantitative real-time PCR (qRT-PCR) technology.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Presently, there is no objective and quantifiable tool to tract progression of PD. Here, using serum miRNAs (stable and measurable molecular analyte) and the unique DATATOP samples (early, untreated PD with baseline and 1–2 year endpoint), we aim to develop robust and multiple biomarkers (compared with the traditional one-marker-at-a-time approach) to track PD progression. Our study will provide a new paradigm shift to accelerate PD-progression biomarker discoveries.
Anticipated Outcome:
We anticipate that the expression of endogenous miRNAs can be detected in the DATATOP samples with no significant difference in comparison with “new” samples due to the stable characteristic of miRNAs. We also anticipate a panel of robust 2-4 PD-progression biomarkers to be developed from this project.
Progress Report
microRNAs (miRNAs) are small RNAs that control gene expression and play important parts in cell
development and differentiation. To study the miRNA stability in serum samples, we examined miRNA expression of five frequently-used endogenous controls in samples from the DATATOP (storage period >30 years) and compared them with control samples with 4-7 years of storage period. Although the overall miRNA expression was lower in the DATATOP samples compared with the controls, the differences were not statistically significant. We are currently examining the changes of miRNA expression in DATATOP samples, using miRNA biomarkers which can predict Parkinson’s disease (PD), to see whether they can also be used to track disease progression. The sample set is divided into two groups according to the rate of their progression: slow and fast progressors. So far, the most current results show no statistically significant X differences in two miRNA biomarkers. In general, the expression of miRNAs is higher at the beginning of sample collection (baseline, year 0) than those collected later (endpoint, year 1.5 to 2). One miRNA, miR-626, shows much higher expression at baseline in fast progressors as compared to slow progressors.
Presentations & Publications
Up-to-date results from this award was included in Khoo’s oral presentation entitled “Circulating microRNAs in plasma as predictive biomarkers for Parkinson’s disease: a new paradigm” (also Chairperson of MicroRNA as Disease Biomarkers session) for the 10th Annual microRNA as Biomarkers and Diagnostics conference in Boston, March 17-18, 2014.
June 2014