# Diversification of Glomerular Kidney Disease Treatments By Targeting Therapeutics to the Kidney

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2023 · $367,900

## Abstract

ABSTRACT
Novel approaches to the treatment of glomerular kidney diseases are needed given that they represent the
third most common cause of end stage renal disease. Systemic lupus erythematosus induced kidney disease
(SLEN) is one glomerular disease where up to 60% of patients exhibit significant declines in kidney function,
resulting in end stage renal disease in ~20%. Although novel treatments are being explored for lupus, they
generally do not benefit the majority of patients and cause systemic immunosuppression, leaving the majority
of the population with less effective treatment options. Additionally, neither new nor old treatments have been
evaluated for their ability to target to the kidney and achieve sufficient exposure to influence the localized
disease processes. The development of novel and effective renal targeted treatment approaches for
glomerular kidney diseases, including SLEN, are needed to meet the clinical efficacy and safety needs
of patients with these disorders. We have recently published research for enhanced kidney deposition of
imatinib in a murine model of SLEN, when formulated in a nanoemulsion developed to optimize kidney
exposure. Results from our studies showed three-fold higher kidney deposition of imatinib in MRL/MpJ-Faslpr
mice that received our novel nanoformulation vs. free drug. We will now test the novel imatinib formulation after
chronic dosing to evaluate efficacy and safety in two mouse models of SLEN. We will also modify this
formulation by linking a relevant ligand or an antibody fragment to target a receptor and protein, respectively,
that are upregulated in glomerular mesangial cells in SLEN. We will test whether these formulation
techniques applied to the existing nanoemulsion will enhance imatinib glomerular deposition and
retention, improve selectivity for targeting mesangial cells, improve therapeutic efficacy and provide
relative safety, as compared to our primary formulation. The central hypotheses of our research are that
1) promising SLEN treatments can be formulated to enhance delivery to the diseased kidney and targeted
structures, and 2) animal models that represent human SLEN will demonstrate favorable treatment responses,
pharmacokinetics, and enhanced safety with imatinib nanoformulations vs. free drug. The research team
comprised of scientists with diverse backgrounds in glomerular kidney diseases, drug development,
nanoformulations, toxicology, and renal pathology across schools at the University of Colorado Anschutz
Medical Center, will synergize their efforts to successfully develop novel strategies to enhance kidney delivery
and accumulation of therapeutics for the treatment of glomerular kidney diseases.

## Key facts

- **NIH application ID:** 10808617
- **Project number:** 1R21AR082655-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** MELANIE S JOY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $367,900
- **Award type:** 1
- **Project period:** 2023-09-22 → 2025-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808617

## Citation

> US National Institutes of Health, RePORTER application 10808617, Diversification of Glomerular Kidney Disease Treatments By Targeting Therapeutics to the Kidney (1R21AR082655-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10808617. Licensed CC0.

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