# Characterizing spatio-temporal changes in immune cell landscapes of multiple sclerosis patients in response to B cell depletion with Ocrelizumab

> **NIH NIH F32** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $64,926

## Abstract

Project Summary
 Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects 2.3
million people globally. MS was traditionally thought to be a T cell mediated disease since autoreactive T cells,
a kind of immune cell, against myelin has been found and their role carefully studied in mouse models of MS.
However, B cell depleting therapies have had excellent clinical success in treating MS, suggesting a key role
for B cells, another kind of immune cell, in MS disease. However, it is unclear how these therapies affect other
key immune cells in the blood or in the cerebrospinal fluid (CSF), the fluid that bathes the CNS.
Characterization of these changes is crucial to understanding how these therapies work and determining if
more targeted approaches can be developed.
 Our goal is to characterize the full repertoire of cells in the CSF and blood of MS patients, and
determine how these populations are altered longitudinally by treatment with Ocrelizumab. By leveraging a
unique therapeutic opportunity, we will identify the spatiotemporal shifts that occur in response to decreased
frequencies B cells. To accomplish our goal, we will: 1) Define the composition of CSF as compared to blood
from healthy and MS donors, 2) track single cell alterations in blood and CSF of MS patients over the course of
Ocrelizumab treatment, and 3) develop and implement unique computational analyses to identify cell states
and genes that correlate with disease, treatment, and anatomical compartment. We propose to implement a
new method for analyzing single cells, called Seq-Well, which will allow us to transcriptionally profile thousands
of single cells in parallel. This method is well suited for profiling rare and low input clinical samples like those
from CSF. We hypothesize that alterations in the total pool of B cells will lead to global changes in the immune
cell landscape, and specifically, will impact the frequency and transcriptional state of T cells.
 This work is fundamental to human health because it will shed light on the mechanism of B cell
depleting therapies, should enable the development of immune monitoring strategies, and will refine models of
CNS-peripheral cross talk. Specifically, our work will also identify key gene modules underlying clinically
relevant axes, potentially suggesting better biomarkers and treatment paradigms while improving our
understanding of immune system dysfunction in MS. Finally, the unique data sets and analyses that will be
generated as part of this work will contribute broadly to our understanding the CSF and result in new analytical
pipelines that integrate various forms of single-cell data.

## Key facts

- **NIH application ID:** 9850198
- **Project number:** 5F32AI136459-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Brittany Anne Goods
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 5
- **Project period:** 2018-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850198

## Citation

> US National Institutes of Health, RePORTER application 9850198, Characterizing spatio-temporal changes in immune cell landscapes of multiple sclerosis patients in response to B cell depletion with Ocrelizumab (5F32AI136459-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9850198. Licensed CC0.

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