Abstract Details

Title Circulating microRNAs as Biomarkers for Disease Staging in MS

Topic MS and Related Diseases

Presentation(s) S11 - (-)

Poster/Presentation
Number 005

Objective

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.

Authors/Disclosures
Roopali Gandhi, PhD (Sanofi Genzyme) PRESENTER	No disclosure on file
Brian C. Healy	The institution of Mr. Healy has received research support from Analysis Group. The institution of Mr. Healy has received research support from Bristol-Myers Squibb. The institution of Mr. Healy has received research support from Verily Life Sciences. The institution of Mr. Healy has received research support from Novartis. The institution of Mr. Healy has received research support from Merck Serono. The institution of Mr. Healy has received research support from Genzyme.
Taha Gholipour, MD (UC San Diego Health - Comprehensive Epilepsy Center)	Dr. Gholipour has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Samia J. Khoury, MD, FAAN (Nehme and Therese Tohme MS Center)	Dr. Khoury has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merk. Dr. Khoury has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Khoury has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for ANA. Dr. Khoury has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Clinical Immunology. The institution of Dr. Khoury has received research support from MENACTRIMS. The institution of Dr. Khoury has received research support from NMSS. The institution of Dr. Khoury has received research support from Office of Naval Research USA. An immediate family member of Dr. Khoury has received intellectual property interests from a discovery or technology relating to health care.
Francisco J. Quintana, PhD (Brigham and Women's Hospital/Harvard Medical)	Dr. Quintana has nothing to disclose.
Benjamin M. Greenberg, MD, FAAN (UT Southwestern Medical Center)	Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Greenberg has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Clene. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IQVIA. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abcuro. Dr. Greenberg has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Siegel Rare Neuroimmune Association. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Husch Blackwell. Dr. Greenberg has stock in GenrAb. Dr. Greenberg has stock in Clene. The institution of Dr. Greenberg has received research support from Anokion. The institution of Dr. Greenberg has received research support from Regeneron. Dr. Greenberg has received intellectual property interests from a discovery or technology relating to health care. Dr. Greenberg has received publishing royalties from a publication relating to health care.
	No disclosure on file
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Siemens. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Academic CME. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche. The institution of Dr. Chitnis has received research support from Tiziana Life Sciences. The institution of Dr. Chitnis has received research support from Bristol-Myers Squibb. The institution of Dr. Chitnis has received research support from Wesley Clover.
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..

��ɫ��

��ɫ��