# Investigation of urinary extracellular vesicles as novel and safe therapeutics for autosomal recessive polycystic kidney disease

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $465,690

## Abstract

ABSTRACT
Autosomal recessive polycystic kidney disease (ARPKD) is a leading cause of kidney failure in childhood and is
caused primarily by mutations in the PKHD1 gene as well as mutations in CYS1. Although ARPKD patients
progress to end stage kidney disease at varying ages, 20-30% of ARPKD patients have severe disease which
results in death 24-48 hours after birth. Despite the tremendous unmet need, limited progress has been made
for ARPKD treatment and no FDA-approved therapies are available for ARPKD patients. Although tolvaptan, a
small molecule drug that was approved in 2018 for autosomal dominant PKD which mostly affects adults, is
currently under phase I clinical trials for ARPKD, tolvaptan is not kidney-targeted and results in off-target effects.
Additionally, tolvaptan’s long-term efficacy, tolerability, and developmental consequences in a primarily pediatric
ARPKD patient population and its ability to enhance survival in neonates with severe ARPKD is unknown. Thus,
new therapeutic strategies that can address both safety and efficacy in ARPKD are urgently needed. To that
end, the purpose of this proposal is to examine the potential of urinary extracellular vesicles (uEVs) as a novel
and safe therapy for ARPKD. EVs, also known as exosomes, are secreted, membrane-bound, biological
nanoparticles that facilitate cell-to-cell communication and contain RNA and protein cargo characteristic to their
parent cell. We propose uEVs for ARPKD therapy for several reasons: uEVs are 1) inherently biocompatible
which is critically important when developing therapies for pediatric patients, 2) carry fibrocystin and cystin, the
gene products of PKHD1 and CYS1 which are mutated in ARPKD, respectively, 3) have been found to home to
the kidneys and transfer functional proteins to induce a therapeutic outcome in kidney disease, and 4) obtaining
high quantities uEV from urine, which is normally discarded, is feasible, noninvasive, and cheap. We hypothesize
that uEVs derived from non-disease sources are a safe therapy that can be used to deliver and supplement
functional proteins including fibrocystin and cystin that are defective in ARPKD to inhibit disease progression. To
test our hypothesis, we will first characterize the nanoparticle properties of uEVs and evaluate uEV fibrocystin
and cystin protein and mRNA cargo, cell internalization, and therapeutic effects in renal cells in vitro (Aim 1).
Next, we will administer uEVs intravenously in slowly progressing and severe ARPKD murine models and
evaluate the pharmacokinetic properties, therapeutic efficacy, and safety in vivo (Aim 2.1). Finally, given most
human ARPKD leads to death in utero or in newborns shortly after birth, we will deliver uEVs in utero in pregnant
mice and evaluate the ability to extend survival in severe ARPKD upon fetal delivery (Aim 2.2). Through our
multidisciplinary, investigative team of nanomedicine and pediatric nephrology, we are well-equipped and fully
committed to successfully car...

## Key facts

- **NIH application ID:** 10750704
- **Project number:** 1R21HD113263-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Eun Ji Paige Chung
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $465,690
- **Award type:** 1
- **Project period:** 2023-09-04 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10750704

## Citation

> US National Institutes of Health, RePORTER application 10750704, Investigation of urinary extracellular vesicles as novel and safe therapeutics for autosomal recessive polycystic kidney disease (1R21HD113263-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10750704. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*