# Protein-polymer nanomedicine for Sjogren's Syndrome

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $412,500

## Abstract

Sjögren's syndrome (SS) is an autoimmune disease affecting more than 4 million Americans, over 90% of
whom are women. SS is characterized by lymphocyte infiltration of lacrimal and salivary glands leading to dry
eye and dry mouth, and resulting in severely compromised ocular surface and oral health. Some patients with
SS also exhibit weight loss, fatigue, internal organ failure, and B-cell lymphoma. Despite its prevalence and
severity, there are no approved therapies for treatment of SS. Treatments are based on management of ocular and
oral dryness as well as use of general immunosuppressive drugs which are not optimized for the underlying
autoimmune exocrinopathies. Although not developed for SS, RestasisT™, an ophthalmic emulsion of
cyclosporine A approved for dry eye, has been explored for use in SS-mediated dry eye. While modestly
effective in treating ocular surface symptoms, Restasis™ does not restore tear production. This is unsurprising
because the nasolacrimal ducts efficiently drain drugs administered topically, limiting drug access to the
lacrimal gland and to other sites of systemic inflammation. Systemic administration of cyclosporine A and
rapamycin, another potent immunosuppressant, has been challenging because of their low solubility, poor
bioavailability and dose-limiting toxicities. Surprisingly, no attempts have been made in SS to deliver these
immunosuppressants to inflamed lacrimal or salivary glands using state-of-the-art drug carriers. Such a
strategy could not only treat the origin of the severe ocular and oral cavity symptoms at their source, but also
potentially mitigate the systemic and life-threatening complications of the disease. The goal of this project is
to enhance the activity of these two clinically-approved immunosuppressants to treat inflamed lacrimal
and salivary glands and other sites of disease activity in SS through use of an emerging class of
`protein polymer' nanomedicines based on elastin-like polypeptides (ELPs) to develop untargeted and
targeted drug carriers. Our preliminary studies show that rapamycin administered intravenously in a novel
protein nanoparticle in a mouse model of SS reduced lacrimal gland inflammation and restored function, while
suppressing the renal toxicity associated with free drug. We propose three SPECIFIC AIMS: 1) Optimize the
route of administration of untargeted ELP drug carriers using murine models of SS; 2) Construct and
evaluate molecularly-targeted immunosuppressive ELP nanoparticles using murine models of SS; and
3) Complete comparative pharmacokinetics and toxicology of optimal therapies for local and systemic
SS. When successful, this translational project will produce a significant advance in drug delivery technology
by generating protein-polymer nanoparticles decorated with proteins that specifically carry rapamycin and
cyclosporine A, and can be targeted to sites of inflammation. Our experiments will lay the solid preclinical
foundation justifying further investmen...

## Key facts

- **NIH application ID:** 9873032
- **Project number:** 5R01EY026635-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Sarah F Hamm-Alvarez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873032

## Citation

> US National Institutes of Health, RePORTER application 9873032, Protein-polymer nanomedicine for Sjogren's Syndrome (5R01EY026635-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873032. Licensed CC0.

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