MicroRNAs (miRNAs) are small regulatory RNAs controlling gene expression. We have recently reported reduced miRNAs levels in serum from Parkinson disease (PD) patients, and also from patients with idiopathic rapid-eye-movement (REM) sleep behavior disorder (IRBD) - a condition that eventually evolves into PD - years before the appearance of the motor symptoms (Fernández-Santiago et al. Ann Neurol 2015). Here we aim to expand previous association findings by quantifying serum miRNA expression levels in a cohort of subjects at-risk to develop PD encompassing healthy individuals carrying the G2019S mutation in the LRRK2 gene (here termed LRRK2 assymptomatic carriers).
Reduced expression of specific serum miRNAs are predictive of the appearance and progression of the motor symptoms in PD and could contribute to the early identification of individuals that, being yet healthy, are close to develop motor PD.
(1) Longitudinal study: The miRNA expression of three miRNA candidates will be studied longitudinally in LRRK2 assymptomatic carriers followed-up every 12- to-18 months over 3-to-4.5 years until the moment of appearance of motor symptoms (conversion to PD). Ultimately we intend to monitor disease progression and PD diagnosis in these subjects.
(2) Cross-sectional study: Hundreds of novel miRNAs will be analyzed in LRRK2 assymptomatic carriers and patients with manifest PD at one-time point. Here we aim to identify new candidate miRNAs biomarkers of early and/ or manifest PD.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Exploring the prodromal stage of PD is important to understand the earliest disease events and to eventually find the urgently needed diagnostic and disease progression biomarkers. We intend to identify miRNA biomarkers able predict disease progression and detect conversion of LRRK2 assymptomatic carriers into motor PD, potentially providing a new diagnostic tool and opening a window for the early clinical intervention.
Next Steps for Development:
The identification of reliable miRNAs biomarkers of the prodromal stage of PD would aid to monitor the effect of neuroprotective drugs, when available, able to prevent or halt disease progression, thereby implementing a cost effective tool to monitor disease evolution and to assess drug effects in clinical trials.