Blood microRNA-7 as a Progression Biomarker in men with Parkinson's disease (S37.006)

Abstract

<h3>Objective:</h3> To investigate the use of microRNA-7-5p (miR-7-5p) as a potential biomarker for Parkinson9s disease (PD) progression. <h3>Background:</h3> Animal models have shown that MiR-7-5p regulates alpha-synuclein (α-syn) translation, transcription and autophagy, in addition to NLRP3 inflammasome activity. Furthermore, MiR-7-5p is diminished in the substantia nigra and the peripheral blood of PD patients. <h3>Design/Methods:</h3> Data was obtained at two longitudinal points (Baseline and 36 months) from 315 (208 male/107 female) drug-naïve PD patients and 160 (108 male /52 female) age- and sex-matched healthy controls (HC) from the Parkinson9s Progression Marker Initiative (PPMI). Whole blood miR-7-5p was longitudinally correlated with a) clinical assessment tools (MDS-UPDRS motor and total scores), b) markers of inflammation (NLRP3 mRNA, IL-1β mRNA, and NfL), and c) α-syn expression (α-syn mRNA, CSF α-syn). Analyses were done using rmcorr in R. <h3>Results:</h3> MiR-7-5p levels decreased by 17% in PD patients over 36 months. Longitudinal, Ln miR-7-5p had a strong negative correlation with MDS-UPDRS-motor and total scores in men with PD and with NfL for all PD subjects. There was no correlation between miR-7-5p and CSF α-syn protein in either group. <h3>Conclusions:</h3> Our data demonstrate the importance of gender differences in biomarker discovery and suggest a robust association between lower levels of miR-7-5p and markers of clinical progression in men with PD. These findings support the use of miR-7-5p as a progression biomarker, which could lead to a quantifiable tool for disease-modifying therapies. <b>Disclosure:</b> Dr. Schiess has nothing to disclose. Dr. Suescun has nothing to disclose. Dr. Block has nothing to disclose. Dr. Tharp has nothing to disclose. The institution of Prof. Ellmore has received research support from NIMH. The institution of Dr. Shahnawaz has received research support from American Parkinson Disease Association. The institution of Dr. Shahnawaz has received research support from NIH. The institution of Dr. Shahnawaz has received research support from Texas Alzheimer’s Research &amp; Care Consortium . Dr. Shahnawaz has received intellectual property interests from a discovery or technology relating to health care. Dr. Adams has stock in Medtronic.