# POP2 as a novel therapeutic in rheumatoid arthritis

> **NIH NIH R21** · ALBANY MEDICAL COLLEGE · 2022 · $215,160

## Abstract

Project Summary:
Inflammation underlies the disabling manifestations and co-morbidities of rheumatoid arthritis (RA). Treatment
regimens for RA patients aim to control inflammation and progressive joint damage mediated by inflammatory
cytokines including TNFα, IL-1β, and IL-6. Recent studies demonstrate that humans possess four genes
coding Pyrin-only proteins (POPs) that limit NF-B signaling and inflammasome activation pathways, events
critical for elaboration of the cytokines mediating inflammation. TNF, IL-1β, and IL-6 are critically regulated by
NF-B transcription factors. We have previously described the anti-inflammatory properties of POP2 in-vitro
and in-vivo. Here we propose proof-of-concept studies to evaluate how POP2 and POP2-derived peptides
impact experimentally induced RA when administered exogenously, using a murine preclinical model. POP2
peptide therapy represents a novel therapeutic approach to ameliorating excessive inflammation through dual
inhibition of both NF-B signaling and inflammasome pathways. The immunological and molecular basis for
our hypotheses stems from our published and preliminary data showing the naturally expressed, non-toxic
POP2 peptide dampens cytokine production in inflammatory responses without compromising host immunity.
Our studies will provide insight into how treatment regimens based on POP2 peptide therapy may be utilized or
improved upon. In vitro characterization, dose-escalation studies and in-vivo assessment of disease
parameters will inform approaches to develop POP2 peptides as a novel therapeutic.

## Key facts

- **NIH application ID:** 10524468
- **Project number:** 1R21AR080367-01A1
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** JONATHAN A HARTON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $215,160
- **Award type:** 1
- **Project period:** 2022-09-23 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10524468

## Citation

> US National Institutes of Health, RePORTER application 10524468, POP2 as a novel therapeutic in rheumatoid arthritis (1R21AR080367-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10524468. Licensed CC0.

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