Objective: This study investigates the use of microRNA-7-5p (miR-7-5p) as a potential biomarker for Parkinson’s disease (PD) progression.

Background: MiR-7-5 is a microRNA that regulates alpha-synuclein (α-syn) translation, transcription and autophagy. It is diminished in the substantia nigra and the peripheral blood of PD patients[1, 2]. These features make miR-7-5p a potential biomarker for disease progression.

Method: Data from two longitudinal points (Baseline and 36 months) from 346 (229male/123female) drug-naïve PD patients and 158 (109male/52female) age- and sex-matched healthy controls (HC) from the Parkinson’s Progression Marker Initiative was used. Whole blood miR-7-5p was longitudinally correlated with a) MDS-UPDRS motor and total scores, b) whole blood α-syn mRNA, c) CSF α-syn, d) whole blood NLR Family Pyrin Domain Containing 3 (NLRP3) mRNA, e) whole blood interleukin-1 beta (IL-1β) mRNA and f) serum neurofilament light chain (NfL) protein by repeated measures correlation. Analyses were done using rmcorr in R.

Results: MiR-7-5p levels decreased significantly in subjects with PD and healthy male controls longitudinally while remaining unchanged in female controls. A robust negative correlation of miR-7-5p with MDS-UPDRS-motor and total scores was demonstrated in PD males. Repeated measures correlation showed a negative correlation with NfL for PD subjects and a positive correlation with NLRP3 for both PD patients and controls. At 36 months, α-syn mRNA was significantly lower in PD patients than controls and was positively correlated with miR-7-5p in male PD patients and female controls.

Conclusion: Our data highlights the importance of gender differences in biomarker discovery and suggests a significantly greater association between lower levels of miR-7-5p and PD progression in males. These findings support the use of miR-7-5p as a progression biomarker in male PD patients, which could lead to a quantifiable tool for disease-modifying therapies.

References: 1. McMillan, K.J., et al., Loss of MicroRNA-7 Regulation Leads to alpha-Synuclein Accumulation and Dopaminergic Neuronal Loss In Vivo. Mol Ther, 2017. 25(10): p. 2404-2414.
2. Kern, F., et al., Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during Parkinson’s disease progression. Nature Aging, 2021. 1(3): p. 309-322.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/blood-microrna-7-as-a-progression-biomarker-in-parkinsons-disease/