# Cortical Demyelination and Repair in Early Multiple Sclerosis.

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $667,644

## Abstract

PROJECT SUMMARY/ABSTRACT
Multiple Sclerosis (MS) is an immune-mediated, demyelinating disorder of the central nervous system (CNS)
and a leading cause of disability in young adults. MS white matter lesions are easily visible on clinical magnetic
resonance imaging (MRI) and are the target of current treatments. However, white matter lesions are poor
predictors of disability, and prevention of white matter lesion formation does not stop gradual disability worsening
in later stages of disease, when white matter lesion formation is rare. Cortical lesions are also common in MS,
can be extensive, and are associated with disability and disability worsening over time. Cortical lesions are
thought to form due to overlying meningeal inflammation and thus they may respond differently to treatment than
white matter lesions, in which inflammatory mediators come from parenchymal veins. Here we propose to further
our understanding of MS cortical lesion formation and repair in early MS, the immunological mechanisms
underlying these processes, and the impact of these processes on the clinical course of disease.
New MRI methods applied at ultra-high field strength (7 tesla, T), some of which we helped to develop, now allow
us to sensitively visualize cortical lesions in vivo and track their formation and repair. With these methods, we
and others have demonstrated that cortical lesions are common, even early in disease, and are associated with
disability. We have also found that cortical lesion burden, but not white matter lesion burden, predicts subsequent
worsening of motor disability. Our recent data demonstrate that cortical lesion formation is rare in longstanding
disease, and so we hypothesize that cortical lesions form early in disease and then lead to subsequent gradual
worsening of disability over time. Here, we propose to follow a cohort of adults with newly diagnosed MS for 3
years with 7T MRI (including 0.5mm3 T1 and motion and B0-corrected T2* weighted imaging), motor and cognitive
evaluation, and blood collection at baseline, year 1, and year 3. A subset of participants will also undergo
cerebrospinal fluid (CSF) collection at baseline. We will determine how cortical and white matter demyelination
are related in early MS and their relative contributions to physical and cognitive disability and disability worsening
over time (Aim 1). Using annual MRI data as well as data from short interval MRI follow-up (baseline, month 3,
month 6) in a subset of participants, we will measure changes in cortical lesions over time and characterize
cortical lesion growth, repair, and chronic inflammation (Aim 2). Finally, we will use single cell transcriptomics,
proteomics, and flow cytometry in blood and CSF to determine how cortical lesion burden is related to immune
activation in the periphery and the CNS (Aim 3).
This work will lead to key advances in our understanding of the pathophysiology, natural history, and clinical
implications of cortical lesions in early MS...

## Key facts

- **NIH application ID:** 10945252
- **Project number:** 1R01NS138611-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Erin Savner Beck
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $667,644
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10945252

## Citation

> US National Institutes of Health, RePORTER application 10945252, Cortical Demyelination and Repair in Early Multiple Sclerosis. (1R01NS138611-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10945252. Licensed CC0.

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