# Treatment of Knee Osteoarthritis via Intra-articular Delivery of an Immunosuppressive Enzyme

> **NIH AR R01** · UNIVERSITY OF FLORIDA · 2026 · $578,489

## Abstract

Project Summary
 In osteoarthritis (OA), intra-articular inflammation is a key mediator of joint destruction and chronic joint pain.
Unfortunately, current strategies to control joint inflammation have largely failed. To address this challenge, our
team is developing an innovative metabolic reprogramming strategy for the treatment of knee OA. In our strategy,
indoleamine 2,3-dioxygenase (IDO), an immunosupressive enzyme, will be intra-articularly delivered to
catabolize tryptophan into kynurenines. Based on IDO’s effect in other tissues, this redirection of tryptophan
metabolism will likely drive the polarization of joint-level immune cells toward an anti-inflammatory state.
Importantly, our strategy differs from other intra-articular delivery strategies for protein and synthetic drugs, as
our enzyme will continuously produce anti-inflammatory metabolites in the OA-affected joint and thereby create
prolonged anti-inflammatory effects that potentially reset immune homeostasis in the joint. However, while IDO
can continuously produce anti-inflammatory metabolites, free IDO is subject to joint clearance. To address this
challenge, we will also fuse IDO to a carbohydrate-binding protein, thereby extending IDO’s joint residence time
via a novel tissue anchoring approach. Morever, because tissue-anchored IDO does not need to release to
generate anti-inflammatory signals, the anchored IDO will continue to produce anti-inflammatory kyneurenines
without the need for our ‘drug’ (IDO) to release and bind a specific target. Our preliminary data demonstrate that
tryptophan metabolism is altered in both human OA and rodent models, our tissue anchoring strategy can extend
the residence time of an enzyme from a few days to over 4 weeks, and that intra-articular delivery of an IDO
fusion protein can shift tryptophan metabolism, reduce inflammation, and reverse pain-related behaviors in a rat
knee OA model. As such, this R01 proposal seeks to evaluate intra-articular delivery of an I

## Key facts

- **NIH application ID:** 11334277
- **Project number:** 5R01AR079874-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Kyle D Allen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AR
- **Fiscal year:** 2026
- **Award amount:** $578,489
- **Award type:** 5
- **Project period:** 2022-04-01T00:00:00 → 2027-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11334277

## Citation

> US National Institutes of Health, RePORTER application 11334277, Treatment of Knee Osteoarthritis via Intra-articular Delivery of an Immunosuppressive Enzyme (5R01AR079874-05). Retrieved via AI Analytics 2026-07-09 from https://api.ai-analytics.org/grant/nih/11334277. Licensed CC0.

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