# Spatiotemporal tuning of myelin antigens and rapamycin for enhanced antigen-specific immune tolerance in multiple sclerosis.

> **NIH NIH R43** · STATERA THERAPEUTICS INC. · 2021 · $295,051

## Abstract

Project Summary
Multiple sclerosis (MS) is an autoimmune disorder thought to be caused by the self-attack on
myelin sheath by autoreactive T cells. Despite improvements in technologies to temporarily
suppress the immune system to mitigate the recurrence of MS attacks, there is no current solution
that addresses the underlying autoimmune response in MS. For instance, existing injectable
therapies such as beta-interferons are only temporary, lasting only about six months. While
ocrelizumab is the first CD20 therapeutic antibody to show an effect in progressive MS, its
clinical effects are rather modest, only showing a 6% reduction compared to placebo in both 12
and 24 week disability progression. Development of approaches that direct re-education of
the immune system to be tolerogenic to self-antigens in MS is therefore an unmet need. In
order to generate selective specific immune tolerance to myelin autoantigens, combinatorial
delivery of antigen and immunosuppressive drugs (e.g. rapamycin) to antigen presenting cells is
a powerful approach. However, dual delivery of antigen and rapamycin raises spatial and
temporal considerations, as localization (space) and sequence (time) of antigen/rapamycin can
dictate the magnitude of cis-priming of antigen presenting cells. To prime antigen presenting
cells more efficiently by maneuvering the favorable spatiotemporal modality of rapamycin and
antigen, we previously formulated a novel nanocarrier platform, Spatiotemporally Tuned
Particle (STP), that delivers rapamycin and antigen specifically to antigen presenting cells in a
preferred sequence. Our ability to tune the spatiotemporal delivery of antigen and rapamycin
resulted in significant improvement of immune tolerance in mice, expanding Tregs and
improving clinical symptoms in experimental autoimmune encephalomyelitis (EAE). In this
program, we will utilize our promising platform to generate myelin autoantigen specific
tolerance in EAE induced by multiple antigens found in the myelin sheath of spinal cord
homogenate, which is representative of MS in humans. In aim 1, we fabricate and characterize
STP candidates encapsulating myelin peptides and rapamycin. In aim 2, we validate the
therapeutic efficacy of STP candidates in spinal cord homogenate EAE and investigate antigen-
specificity and immune cell infiltration. Overall, our proposed approaches will ultimately allow
researchers to leverage our platform for targeted and sequential delivery of multiple therapeutic
agents to unlock their full potentials in MS and other autoimmune diseases.

## Key facts

- **NIH application ID:** 10325547
- **Project number:** 1R43AI157959-01A1
- **Recipient organization:** STATERA THERAPEUTICS INC.
- **Principal Investigator:** Joseph J Catino
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $295,051
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-06-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10325547

## Citation

> US National Institutes of Health, RePORTER application 10325547, Spatiotemporal tuning of myelin antigens and rapamycin for enhanced antigen-specific immune tolerance in multiple sclerosis. (1R43AI157959-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10325547. Licensed CC0.

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