Abstract Details

Title Stool GFAP Is Elevated in Progressive MS, Is Associated with Disability, and Predicts Disease Worsening

Topic Multiple Sclerosis

Presentation(s) S42 - Multiple Sclerosis: Biomarkers/Neuroimaging (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Background The gut microbiome is abnormal in MS and can influence disease via many pathways. Serum NfL and GFAP are elevated in MS and are linked to neuronal and glial abnormalities in the brain. The gut is a prime target for biomarker discovery given that the gut contains enteric glia which express glial fibrillary acidic protein (GFAP) and regulate enteric nervous and immune function.

Objective Investigate stool protein biomarkers as predictive of disease worsening in multiple sclerosis (MS).

Design/Methods Stool was analyzed from 26 healthy controls (HC), 61 RRMS and 28 progressive MS (ProgMS) subjects via enzyme linked immunosorbent assay (ELISA) to GFAP. Subjects had clinical follow-up 2-years after stool donation, including EDSS, symbol digit modality testing (SDMT), and NeuroQoL measurement.

Results

Stool GFAP was significantly higher in ProgMS subjects by 86.9% and 103.1% compared to RRMS and HCs respectively (F(2,112) = 29.08, p < 0.0001). Further, stool GFAP level was positively correlated with baseline EDSS (rho = 0.589, p < 0.0001) and with an increased EDSS at 2-years (rho = 0.268, p < 0.05). Stsool GFAP levels were significantly correlated with worsening in seven NeuroQoL domains: upper and lower extremity function, ability to participate in and satisfaction with social roles, stigma, cognitive function, and anxiety. GFAP trended towards a negative correlation with baseline SDMT score (rho = -0.23, p = 0.052), which was significant at 2-years (rho = -0.26, p < 0.05). Neither stool NfL nor multiple inflammatory markers were altered in MS.

Conclusions Stool GFAP is a biomarker for ProgMS with prognostic value for EDSS, SDMT, and NeuroQoL, and may serve as biomarker linked to disease stage and course. Enteric glial signaling is a novel avenue for the study of the role of the microbiome in MS and may be linked to peripheral immune activation.

Authors/Disclosures
Luke Schwerdtfeger, PhD (Brigham and Women's Hospital) PRESENTER	Dr. Schwerdtfeger has nothing to disclose.
Federico Montini (Brigham and Women's hospital - Harvard Medical School)	Mr. Montini has nothing to disclose.
Millicent Ekwudo	No disclosure on file
Bonnie Glanz (Brigham and Women'S Hospital)	The institution of Ms. Glanz has received research support from CMSC. The institution of Ms. Glanz has received research support from NIH.
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 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.
Laura M. Cox (Harvard Medical School)	No disclosure on file
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..