# Intra-Lymph Node Delivery of Tolerogenic Microparticles for Modulating Disease in a Model of Multiple Sclerosis

> **NIH NIH F31** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $32,002

## Abstract

PROJECT SUMMARY
Multiple Sclerosis (MS) is a debilitating disease that occurs when the body’s immune system incorrectly recognizes myelin,
the matrix that insulates neurons in the central nervous system (CNS) as foreign. Current treatments for MS aim to reduce
the severity of disease, but do not treat the cause, and require continual, frequent treatments over the lifetime of the patient
to maintain disease remission, though the disease ultimately will progress. Unfortunately, these existing therapy options are
also non-specific – they cannot differentiate between myelin-specific inflammatory immune cells and other lymphocytes,
leaving patients susceptible to opportunistic infections. Myelin-specific inflammatory cells are activated in lymph nodes
(LNs), sites which coordinate immune cell interactions that control immune cell phenotypes. In the LNs, antigen presenting
cells, including dendritic cells (DCs), present antigens – such as myelin in MS – to T and B cells. Depending on the signals
present during this interaction, T cells can become inflammatory effector cells or regulatory cells (TREGS) that control the
activity of inflammatory cells. During MS, these myelin-specific effector cells contribute to inflammation and
neurodegeneration in the CNS. To overcome the limitations of current treatments, this proposal focuses on developing
therapies that promote selective immune tolerance to myelin by inducing antigen-specific TREGS that can selectively control
disease. To meet this goal, a direct LN injection technique will be used to deposit polymer particles co-loaded with myelin
self-antigens and rapamycin, an immunomodulator, in LNs of mice induced with a relapsing-remitting model of MS. Studies
have shown that the presence of Rapamycin, during the priming of a T cell can promote TREGS. Our lab has shown that a
single injection of particles into LNs allows local programming of the LN microenvironment to promote TREGS, which
permanently stopped and reversed disease-induced paralysis in a model of progressive MS. However, 85% of patients
initially present with the relapsing-remitting form of MS, in which the immune system becomes reactive to different sections
of myelin over time. This epitope spreading complicates treatment regimens, and therapies do not consistently work at all
stages of disease. Thus, a relapsing-remitting model will allow for the study of epitope spreading, and how disease
progresses when protection is conferred to an epitope at an earlier disease stage. Preliminary data shows that treating during
the first wave of disease with a single iLN injection of particles co-loaded with rapamycin and the myelin epitope attacked
during that wave can reverse disease and prevent relapse. This proposal will investigate how treatments at different stages
of disease with different myelin epitopes alters disease progression and prevents relapse.

## Key facts

- **NIH application ID:** 9867516
- **Project number:** 5F31AI143204-02
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Emily A Gosselin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,002
- **Award type:** 5
- **Project period:** 2019-01-30 → 2020-12-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9867516

## Citation

> US National Institutes of Health, RePORTER application 9867516, Intra-Lymph Node Delivery of Tolerogenic Microparticles for Modulating Disease in a Model of Multiple Sclerosis (5F31AI143204-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9867516. Licensed CC0.

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