# Development of a New Treatment for Diabetic Wounds

> **NIH NIH R41** · NUTRIWYO, LLC · 2020 · $241,148

## Abstract

Abstract: Non-healing wounds affect ~25% of people with diabetes and represent a primary cause of
amputation of lower limbs, which is an enormous clinical problem and a substantial economic burden. Given
the lack of approved agents that effectively aid in the healing of diabetic wounds, a major need exists for
developing novel pharmacological agents for treating diabetic wounds. Chronic diabetic wounds are
characterized by a highly proteolytic microenvironment. The elevated proteolytic activity leads to a continuous
breakdown of the extracellular matrix proteins such as collagen, sustaining a prolonged destructive state that
delays wound-healing. Cathepsin K is the most potent mammalian collagenolytic enzyme known. Preliminary
studies show that skin tissues from diabetic human subjects have lower levels of collagen and elevated levels
of the cathepsin K compared to the skin from non-diabetic humans. Furthermore, cathepsin K is upregulated in
the skin tissue from diabetic mouse, and pharmacological inhibition of cathepsin K accelerated wound-healing
in the diabetic pig model, providing a strong rationale for this project. The overall goal of this Phase I STTR
project is to develop/validate/commercialize a new approach to treat diabetic wounds by using a potent, and
selective inhibitor of cathepsin K that has previously undergone clinical trials for other application. The Specific
Aims of this Phase I feasibility project are to 1) Determine the efficacy of intradermal injection of the cathepsin
K inhibitor in healing diabetic wounds in a translationally relevant porcine model of diabetic wound-healing, and
2) Evaluate molecular changes in the diabetic wound in response to treatment with the cathepsin K inhibitor.
We will determine the percent wound closure with five predetermined doses of the inhibitor and compare it with
Regranex® gel (an FDA approved growth-factor for treating diabetic wounds) and vehicle at days 3, 7, 15, and
full closure (~day 21) in both diabetic and non-diabetic pigs. Treatment with the inhibitor (0.3-30ng/mm2 wound
area) is expected to induce complete reepithelization (100% wound closure) by post-wounding day 15.
Furthermore, at the molecular level, we will assess the degree to which treatment with the inhibitor will reduce
epithelial gap, lower cathepsin K levels, increase collagen content, and augment angiogenesis in the wound
on day seven following wounding, as compared to Regranex® and vehicle treatment. A >50% change from
vehicle-treated wounds in the aforementioned parameters will be considered as molecular validation for
accelerated healing by the inhibitor, whereas a >25% change in these parameters compared to Regranex®
would be deemed as ‘superior’ outcome. We anticipate this Phase I STTR project will significantly build upon
the strong preliminary data to establish concept feasibility and to set the stage for a Phase II STTR project
designed to validate the potential for clinical efficacy and, ultimately, product c...

## Key facts

- **NIH application ID:** 10081437
- **Project number:** 1R41DK125213-01A1
- **Recipient organization:** NUTRIWYO, LLC
- **Principal Investigator:** SREEJAYAN NAIR
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $241,148
- **Award type:** 1
- **Project period:** 2020-09-04 → 2022-09-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10081437

## Citation

> US National Institutes of Health, RePORTER application 10081437, Development of a New Treatment for Diabetic Wounds (1R41DK125213-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10081437. Licensed CC0.

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