# Protein-polymer nanomedicine for Sjogren's Syndrome

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $49,157

## Abstract

Project Summary (Parent Award)
Sjögren's syndrome (SS) is an autoimmune disease manifesting with severe inflammation and loss of function
of lacrimal (LG) and/or salivary (SG) glands, leading to severe dry eye and dry mouth. SS patients also exhibit
extraglandular systemic symptoms including development of autoantibodies, inflammation of visceral organs and
increased risk of B-cell lymphoma. Pathogenesis is complex and involves interplay between the activated
immune system and exocrine epithelia; thus, SS therapies should ideally achieve both local glandular and
systemic immunomodulation to fully treat the disease. Our initial focus is developing an effective treatment
regimen for SS-associated dry eye disease (DED) and systemic symptoms, using the male NOD mouse which
exhibits these disease manifestations of SS. We later explore efficacy in a model of autoimmune sialoadenitis
and systemic symptoms, the female NOR mouse. Topical treatments are currently used clinically to manage
symptoms of SS-associated DED, but these approaches are insufficient to suppress LG inflammation. Systemic
symptoms are also treated to limited success with general immunomodulatory agents which also lack sufficient
bioavailability to treat glandular inflammation. We hypothesize and test that a combined approach of
optimized local glandular plus systemic delivery of therapeutics is necessary to effectively treat both
glandular and extraglandular symptoms of SS. To achieve this, we use a versatile protein-polymer platform
comprised of elastin-like polypeptides (ELPs) that can be genetically fused to peptides/proteins in ways that
optimize their pharmacokinetics and bioactivity. Three Aims are proposed. Aim 1. Local LG
immunosuppression using Supra-LG Rapa ELP depots and Molecular targeting to ICAM-1. The
immunosuppressant, Rapamycin (Rapa), will be complexed to a depot-forming FKBP12-ELP fusion protein that
sequesters Rapa; this carrier will be further modified to target intracellular adhesion molecule 1 (ICAM-1)
increased in diseased LG in SS. In male NOD mice, efficacy will be assessed when delivered supra-LG towards
SS-associated DED and systemic disease. Aim 2. Th17 immunosuppression using systemic delivery of
extracellular IL-17 receptor ELPs. Elevated IL-17A is linked to SS pathogenesis. We develop soluble and
depot-ELP fusions expressing the extracellular domain of the IL-17 receptor (eIL17R) to form multivalent IL-17A-
sequestering nanoparticles for systemic delivery using subcutaneous (SC, flank) administration. In male NOD
mice, efficacy will be assessed in SS-associated DED and systemic symptoms. Aim 3: Efficacy of local and
systemic combination therapies in glandular and extraglandular symptoms of SS. Efficacy of combination
local + systemic treatments will be assessed using formulations delivered by supra-LG (5FV-Rapa) and SC
(soluble eIL17R-A192). Efficacy will be assessed both in male NOD mice (autoimmune dacryoadenitis/systemic
symptoms) and in female NOR m...

## Key facts

- **NIH application ID:** 11113713
- **Project number:** 3R01EY026635-07S1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Sarah F Hamm-Alvarez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $49,157
- **Award type:** 3
- **Project period:** 2017-03-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11113713

## Citation

> US National Institutes of Health, RePORTER application 11113713, Protein-polymer nanomedicine for Sjogren's Syndrome (3R01EY026635-07S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11113713. Licensed CC0.

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