# Partial Antagonists of IRE1 RNase—‘PAIR’s—to treat Type 1 Diabetes

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $726,915

## Abstract

PROJECT SUMMARY/ABSTRACT
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by hyperglycemia due to progressive
immune-mediated destruction of pancreatic beta cells. Recent work from our laboratories has shown that
hyperactivation of the unfolded protein response (UPR) to ER stress in the immune-targeted beta cells may be
a critical early event in the development of T1D. We have developed novel pharmacological reagents called
`PAIR's that allow us to manipulate components of the UPR. Importantly, first generation versions of small
molecules—called KIRAs— delivered to NOD mice can efficaciously prevent and even reverse diabetes in this
T1D model. Thus, in this collaborative grant we will capitalize on the complementary expertise of the
investigators to optimize these PAIR lead molecules for potency and selectivity, conduct proof of concept
studies using human islets, and perform key enabling steps needed to advance these candidates further into
the clinic for treating human patients with T1D.

## Key facts

- **NIH application ID:** 10239016
- **Project number:** 5U01DK123609-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Dustin J Maly
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $726,915
- **Award type:** 5
- **Project period:** 2019-09-20 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239016

## Citation

> US National Institutes of Health, RePORTER application 10239016, Partial Antagonists of IRE1 RNase—‘PAIR’s—to treat Type 1 Diabetes (5U01DK123609-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10239016. Licensed CC0.

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