# RELIEPH for Interstitial Cystitis

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $386,231

## Abstract

About 7.9 million women and 4.6 million men in the US suffer from interstitial cystitis/bladder pain
syndrome (IC/BPS). For many patients, the currently available treatments are inadequate and prone to
adverse side effects, including potential dependence and abuse of prescription painkillers. An
innovative nonpharmacological approach is proposed here to treat the debilitating condition of
IC/BPS using a newly developed chemical genetics technology called RELIEPH (Receptor
Engineering to Lessen Inflammation-Evoked Pain and Hyperactivity). The technology, which is based
on the same principles as optogenetics and DREADD, will install engineered chloride (Cl–) channels
into urothelial cells and peripheral nociceptors to control bladder hyperactivity and to alleviate pain in
IC/BPS. The central hypothesis is that the expression of non-native Cl– channels in the neuron-like
urothelial cells and in peripheral nerves can dynamically re-set the hypersensitization of the peripheral
afferents without affecting the process of normal nociception. Two different types of “chemical genetic”
designs will be tested in a rat model of IC/BPS. The first type acts passively by sensing inflammatory
conditions such as acidosis in urothelial cells and peri-nerve tissues. Since etiology of IC/BPS is still
unknown and inflammation is not always present, the second type is designed to selectively respond to
small natural chemicals (including metabolites of certain food) that would otherwise have little or
no analgesic action without the engineered Cl– channels. Promising preliminary data have
demonstrated the efficacy of one of engineered channels in treating inflammatory pain and in restoring
three outcome measures (intercontraction intervals, peak micturition pressure, and micturition pressure
threshold) in a rat model of IC/BPS. The specific aims for the proposed new studies are: (1) design
and optimize ligand-gated Cl– channels to be activated or modulated by primary and secondary amines
found in common food; (2) quantify the physiological effects of the engineered Cl– channels in urothelial
cell cultures by measuring ATP release and intracellular Ca2+; (3) devise and optimize effective gene
delivery strategies by bladder instillation and peri-nerve injection using rAAV, liposomes, and
functionalized nanoparticles, and quantify the engineered receptor expression and localization in
urothelial cells and innervating afferents; and (4) evaluate the in vivo treatment efficacies and gene
dose dependence to devise strategies to improve outcomes.
The innovative idea and bold approaches proposed here will lead to the development of fundamentally
new IC/BPS therapy that will greatly and effectively improve chronic pain management and reduce the
risk of prescription drug abuse.

## Key facts

- **NIH application ID:** 9922263
- **Project number:** 5R01DK117383-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** YAN XU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,231
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922263

## Citation

> US National Institutes of Health, RePORTER application 9922263, RELIEPH for Interstitial Cystitis (5R01DK117383-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9922263. Licensed CC0.

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