Abstract Details

Title The Role of Specific Gut Microbiome Populations in Modulating Disease in the SOD-1 Mode of Amyotrophic Lateral Sclerosis (ALS)

Topic General Neurology

Presentation(s) S43 - General Neurology 2 (2:36 PM-2:48 PM)

Poster/Presentation
Number 009

Background While there has been significant progress in understanding the genetic underpinnings of ALS, greater than 90% of cases are sporadic and environmental factors that modulate genetic disease risk are being identified. The gut microbiota contribute to disease pathogenesis of several neurological disorders including Parkinson's disease, multiple sclerosis, and Alzheimer’s disease. We found that high-dose, broad spectrum antibiotics worsened survival in SOD1 mice, suggesting the gut microbiome as a whole protects against disease progression in ALS, but little is known about individual microbes.

Objective To determine the role of specific microbial populations in modulating the disease progression in SOD1 mice using specific antibiotics.

Design/Methods To deplete specific microbial populations, we administered low dose oral vancomycin or metronidazole to SOD1 mice and measured survival, motor function, and neurological score.

Results We found that vancomycin improved survival (p=0.02) and neurological function, implying that the bacterial populations suppressed by the vancomycin have a deleterious effect on disease progression, whereas metronidazole did not impact disease progression. We are currently sequencing the microbiota to study the bacterial populations suppressed by vancomycin vs. metronidazole to identify microbes that may worsen progression in SOD mice.

Conclusions While high-dose antibiotics that deplete the microbiota worsen progression, we found for the first time that a narrower-spectrum approach of administering vancomycin alone can improve survival. This suggests that specific microbial manipulation may be used to modulate the disease course for the treatment of ALS, and that antibiotic selection may be important in the treatment of infections in ALS patients.

Authors/Disclosures
Megha Kaul (Brigham and Women's hospital) PRESENTER	No disclosure on file
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..