Circulating microRNAs as Biomarkers for Disease Staging in MS (S11.005)

OBJECTIVE: To determine if circulating miRNAs could be identified in MS and whether they linked to disease stage and/or disability. BACKGROUND: MicroRNA (miRNAs) are single stranded, small non-coding RNAs that regulate gene expression. Because they are stable in serum, they are being developed as biomarkers for cancer and other diseases. In MS a major challenge is to develop immune biomarkers to monitor the disease. miRNAs have been studied in immune cell populations in MS but not in the circulation. DESIGN/METHODS: 368 miRNAs were measured in plasma in 10 RRMS, 9 SPMS and 9 healthy controls (HC) using an Exiqon array. 23 miRNAs from this discovery set were validated using qPCR in an independent set of 50 RRMS, 51 SPMS, 32 HCs and 15 ALS patients. RESULTS: We identified 6 miRNAs that differentiated RRMS from HC, 1 that differentiated SPMS from HC, and 5 that differentiated RRMS from SPMS. We also found miRNAs linked to EDSS. hsa-miR-92a-1 was identified in the largest number of comparisons. It was different in RRMS vs. SPMS, RRMS vs. HC and showed association with EDSS and disease duration. miR-92 has gene targets involved in cell cycle regulation and cell signaling. The let-7 family of miRNAs differentiated SPMS vs. HC and RRMS vs. SPMS. Let-7 miRNAs regulate stem cell differentiation, T cell activation, activate TLR-7 and are linked to neurodegeneration. hsa-miR-454 differentiated RRMS vs. SPMS and hsa-miR-145 differentiated RRMS vs. HC; both were associated with EDSS. Interestingly, the same circulating miRNAs (let-7 and miR-92) that were differentially expressed in RRMS vs SPMS also differentiated between ALS and RRMS subjects, but were not different between SPMS and ALS, suggesting similar processes may occur in SPMS and ALS. CONCLUSIONS: Our results establish miRNAs as readily accessible circulating blood biomarkers to monitor disease in MS. Supported by: In part by Merck Serono. Disclosure: Dr. Gandhi has received research support from Novartis. Dr. Healy has received research support from Merck Serono. Dr. Gholipour has received research support from Merck Serono. Dr. Egorova has nothing to disclose. Dr. Musallam has nothing to disclose. Dr. Hussain has nothing to disclose. Dr. Nejad has nothing to disclose. Dr. Khoury has received personal compenation for activities with EpiVax, Argos, LifeCycle, TcLand, Wyeth as a consultant. Dr. Quintana has received personal compensation for activities with EMD Serono and Teva Neuroscience. Dr. Quintana has received research support from EMD Serono. Dr. Kivisakk has received research support from Merck Serono. Dr. Chitnis has received personal compensation for activities with Biogen Idec, Novartis, Sanofi-Aventis Pharmaceuticals, EMD-Serono, and Teva Neuroscience. Dr. Chitnis has received research support from Merck Serono. Dr. Weiner has received personal compensation for activities with Biogen Idec, Novartis, Serono, Inc., Teva Neuroscience, GlaxoSmithKline, Inc., Nasvax, Xenoport and Genzyme Corporation as a consultant, speaker and/or participant on an advisory board. Dr. Weiner has received research support from Merck Serono.