# Development of advanced glycation end product (AGE)-breaking enzymes as a novel therapy for the treatment of diabetic kidney disease

> **NIH NIH R43** · REVEL PHARMACEUTICALS INC. · 2024 · $324,015

## Abstract

PROJECT SUMMARY
Diabetic kidney disease (DKD) is a major complication associated with Type 1 and Type 2 diabetes.
Approximately 25% of patients with diabetes develop DKD. DKD is the leading cause of kidney failure and
accounts for 44% of all end-stage renal disease cases. It is associated with heart disease and heart failure,
stroke, and early death. Treatment options for DKD are limited and focus on slowing progression to end-stage
renal disease through glycemic control. Current FDA-approved treatments do not address pathogenic
mechanisms driving the disease.
The pathophysiology of DKD is related to prolonged exposure to high blood sugar, leading to non-specific
glycation of proteins and subsequent formation of toxic advanced glycation end-products (AGEs). Evidence
suggests that accumulation of AGEs in the kidneys plays a role in the vascular complications associated with
diabetes, including DKD. Revel Pharmaceuticals is developing a novel class of therapeutics designed to cleave
one of the most abundant AGEs accumulating in DKD, carboxymethyl-lysine (CML), thus removing a
significant driver of DKD. Using rational design approaches, we have engineered enzymes that cleave free
CML and CML modified peptides.
Our goal in this Phase I grant is to optimize lead drug candidates and demonstrate enzyme activity on
physiologically relevant DKD substrates. Our specific aims are to (1) engineer CML oxidase to efficiently cleave
CML modifications from physiological substrates (2) characterize CML oxidase activity on model proteins &
human tissues. Successful completion of this Phase I SBIR project will yield the first therapeutic enzyme
designed to remove and repair AGE damage in vivo. In Phase II, we will carry out in vivo efficacy and
IND-enabling studies with our collaborators at the National Mouse Metabolic Phenotyping Center to support an
IND submission.

## Key facts

- **NIH application ID:** 10907375
- **Project number:** 1R43DK137624-01A1
- **Recipient organization:** REVEL PHARMACEUTICALS INC.
- **Principal Investigator:** Aaron Cravens
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $324,015
- **Award type:** 1
- **Project period:** 2024-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907375

## Citation

> US National Institutes of Health, RePORTER application 10907375, Development of advanced glycation end product (AGE)-breaking enzymes as a novel therapy for the treatment of diabetic kidney disease (1R43DK137624-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10907375. Licensed CC0.

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