# PKD1 derepression as a potential therapy for Polycystic Kidney Disease

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $545,651

## Abstract

Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is amongst the most common monogenetic
disorders, with an estimated prevalence of 12.5 million people worldwide. Unfortunately, >50% of
ADPKD patients develop end-stage renal failure and treatment options are still limited. Recent
studies point to reduced PKD1 gene dosage as the disease mechanism for many ADPKD patients.
This revelation opens the door to an exciting possibility that reversing PKD1 decline may arrest
ADPKD in these individuals. However, despite the transformative potential, no PKD1-targeting drugs
are under clinical investigation. Our goal in this application is to provide a scientific roadmap for
developing a novel PKD1-boosting therapeutic approach. We propose a novel idea that along with
the germline mutation, inefficient translation of mRNAs produced by the non-inactivated PKD1 allele
also contributes to the lower PKD1 dosage and aggravates ADPKD. This idea emanates from our
preliminary studies, where we found that deleting the cis-inhibitory miR-17 motif from the PKD1 3’-
UTR is sufficient to improve mRNA translation and to raise PC1 levels. In turn, this approach
ameliorates cyst growth in mice and in vitro human ADPKD models. Based on these promising
observations, we propose: (1) using genetic proof-of-principle approaches to study the impact of
PKD1 derepression in ADPKD mouse and human models, and (2) test the feasibility of
oligonucleotides that outcompete and prevent miR-17 from binding to PKD1 as novel therapeutics to
raise PC1 levels.

## Key facts

- **NIH application ID:** 10498765
- **Project number:** 1R01DK133186-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Vishal Patel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $545,651
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498765

## Citation

> US National Institutes of Health, RePORTER application 10498765, PKD1 derepression as a potential therapy for Polycystic Kidney Disease (1R01DK133186-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10498765. Licensed CC0.

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