A novel anti-inflammatoryand anti-oxidant therapy for treating non-healing diabetic foot ulcers

Active Project Grant Awarded Last action

Award ID
R44DK136463
Recipient
Awarding agency
Obligated
$3,075,160

Award facts

Completion date 93% complete
Originally
Place of performance
Arizona, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Delayed or impaired wound healing is a serious complication of diabetes, often leading to lower limb amputations. By 2050, 1 in 3 americans will develop diabetes, and up to 34% of diabetic patients will develop a diabetic foot ulcer (DFU) in their lifetime. Current treatments for dfus include debridement, infection control, maintaining a moist wound environment, and pressure offloading. Despite these interventions, a large number of dfus fail to heal and are associated with a cost that exceeds $31 billion annually. Chronic inflammation and increased oxidative stress have been implicated in the pathogenesis of the diabetic wound healing impairment. We have designed and tested a new therapeutic that synergistically targets both inflammation and oxidative stress using novel cerium oxide nanoparticles (CNP), which possess reactive oxygen species (ROS) scavenging properties, conjugated with an anti-inflammatory microrna mimic (MIR146A) that is deficient in diabetic wounds and inhibits the activation of nfκb-induced pro-inflammatory response. Importantly, our novel patented conjugate CNP-MIR146A efficiently delivers MIR146A into the wound to reduce inflammation and ROS, and accelerate wound healing. We have developed a CNP-MIR146A specifically formulated for intradermal injection (CTX-001) for the treatment of dfus. Our preliminary studies demonstrate that a one-time intradermal administration of CTX-001 to full-thickness wounds fully corrects the wound healing impairment in diabetic mice and elicits a significant 25% improvement in wounds in diabetic pigs, essentially by normalization of inflammation and oxidative stress. Repeated weekly administration can correct the diabetic wound healing impairment, similar to healing in non- diabetic wounds. Following a pre-IND meeting with the FDA and having completed a pilot bulk drug substance cgmp manufacturing of CTX-001, the objective of this direct to phase II application by CERIA therapeutics (CERIA) is to complete cgmp-grade manufacturing and analysis of CTX-001 drug product (specific aim 1) to fulfill IND-enabling studies. Specific aim 2 will confirm the preclinical efficacy of CTX-001 in diabetic (DB/DB) mice and a porcine model of diabetic wound healing; we will assess the role of infection on the efficacy of CTX-001 in mice, and optimize the dose and frequency of administration of CTX-001 to enhance efficacy in the correction of the impaired healing in diabetic pigs. In specific aim 3, we will carry out a dose-range finding acute toxicity study of CTX-001 in both rats and minipigs, followed by IND-enabling repeat dose toxicology studies. In vitro genotoxicity studies and an irritation/sensitization study in guinea pigs will complete safety studies in preparation for first-in-human clinical trials with our lead product.

Transactions

Action Obligated Date
Amendment $0
Amendment $1,034,376
Amendment $1,034,376
Original award $1,006,408

Quick answers

Who received award R44DK136463?

R44DK136463 was awarded to Ceria Therapeutics Inc. by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on January 15, 2024.

How much is award R44DK136463 worth?

$3,075,160 has been obligated on R44DK136463.

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