# Metabolic correlates of disease activity and disability progression in pediatric MS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $279,374

## Abstract

PROJECT SUMMARY
The biological processes contributing to relapses and disability progression in multiple sclerosis (MS) remain
largely unknown. During the past decade, our pediatric MS Network has investigated risk factors in children. We
have discovered that higher saturated fat and lower vegetable dietary intake may independently increase the
risk of relapse in those with the disease. Our preliminary findings, consistent with the association of high fat diet
with higher risk of MS relapse, suggest that higher plasma levels of three acyl-ethanolamides
(endocannabinoids) and docosahexaenoic acid (DHA) may be associated with higher relapse risk in children.
Lipids mediators such as oxylipins and endocannabinoids have immunomodulatory properties and some are
neuroprotective. Their plasma levels are influenced among others by dietary intake, obesity status and genetic
profile. Furthermore, our findings that the tryptophan pathway is associated with the risk of relapse and disease
progression links plausibly to expected changes in short chain fatty acids that we plan to investigate.
Although MS is less common in children, studies in this age group have several important advantages including
less irrelevant exposures and comorbidities that result from aging. With previous NIH and National MS Society
support, we have established a highly collaborative national research group and a unique resource that will be
leveraged in this proposal to test new hypotheses. We propose state-of-the-art untargeted and targeted
metabolomics and lipidomics analyses to determine the association of various plasma and stool lipids and their
mediators with the risk of subsequent relapse, new MRI lesions, and neurologic and cognitive impairment. Each
individual has extensive demographic, clinical, MRI, genetic, food frequency and environmental exposure data.
Analyses will be adjusted for possible confounders such as age, sex, race, ethnicity, socioeconomic profile, use
of disease-modifying therapy, body mass index and serum 25(OH) vitamin D. We will also model the contribution
of various metabolites in the context of adipokines, food frequency, gut microbiome profile and genetic variants
that modulate plasma lipid and mediator levels. This sophisticated modelling including pathway analyses will
establish which of the variables are independent predictors.
Our group of collaborators with expertise in metabolomics, lipidomics, genetics, and environmental risk factors
is in a unique position to significantly advance the understanding of MS pathogenesis. The findings in the
proposed study will unravel biological links between diet, gut microbiome, obesity and MS course. Although
longitudinal association studies do not confirm causality, they are critical to identify putative biological pathways
that may contribute to disease activity and progression. Intervention studies cannot be designed if associations
are unknown. Our proposed investigation has strong potential for clinical tr...

## Key facts

- **NIH application ID:** 10593945
- **Project number:** 5R01NS117541-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** EMMANUELLE LAURENCE WAUBANT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $279,374
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10593945

## Citation

> US National Institutes of Health, RePORTER application 10593945, Metabolic correlates of disease activity and disability progression in pediatric MS (5R01NS117541-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10593945. Licensed CC0.

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