Preclinical Development of EpiReady, a Novel Therapeutic to Treat Nonhealing Diabetic Foot Ulcers
Abstract
This proposal describes the planned preclinical development of EpiReady, a novel therapeutic designed to promote the healing of diabetic foot ulcers (DFU), a life-threatening complication of diabetes. Chronic non-healing ulcers are a significant medical problem for aging military Veterans and the US population in general, frequently leading to hospitalization and substantially contributing to morbidity and mortality. Importantly, the incidence of these wounds is expected to increase as the American population ages. EpiReady tissue is a non-viable, human skin substitute containing enhanced levels of human cathelicidin, a protein that has been shown to possess numerous activities known to be important to wound healing. Cathelicidin is as an antimicrobial peptide, but also has been shown to promote blood vessel formation and regrowth of the epidermis. Cathelicidin is naturally expressed by keratinocyte skin cells in healthy human skin, and its expression is increased in response to tissue injury. Significantly, chronic non-healing wounds exhibit low levels of cathelicidin. Cathelicidin has a novel mechanism of antimicrobial action that makes development of bacterial resistance very difficult. This is particularly important in light of the recent increase in multidrug-resistant bacterial pathogens. EpiReady tissue is manufactured using NIKS keratinocytes stably modified to enhance production of cathelicidin. In addition to cathelicidin, EpiReady contains a spectrum of naturally produced and processed growth factors and antimicrobial peptides that are anticipated to promote wound healing and prevent infection. EpiReady tissue is dried at the end of production to enable storage for extended periods at room temperature to facilitate ease of storage and use. We hypothesize that EpiReady will expedite tissue regeneration in DFU by inhibiting microbial growth and delivering wound healing factors. The preclinical studies proposed would support the submission of an Investigational New Drug (IND) application to the Food and Drug Administration (FDA) for clinical evaluation of EpiReady tissue in humans. This work is broken down into three components. The first task is to perform studies to optimize steps important for the manufacture and performance testing of EpiReady tissues. This work is done by adjusting critical steps and measuring the resulting changes to the tissue properties such as handling characteristics, barrier properties, and protein expression patterns. Prior to human clinical trials, the FDA requires assessment of a cell-based product s efficacy and safety using appropriate animal models. To address these important issues, the next component will evaluate the performance and safety of EpiReady tissue using well-characterized animal models. The final objective of this project is to summarize the work completed in preparation for submission to the FDA. Successful completion of these goals will enable initiation of human clinical trials of EpiReady, with the ultimate goal of obtaining FDA approval and commercialization of this innovative technology. If proven safe and effective, EpiReady tissue has the potential to radically change the prognosis for patients suffering from debilitating, chronic, infected wounds. Ideally treatment with EpiReady tissue would accelerate wound healing, reduce infection, reduce the rate of wound reoccurrence, improve functional outcomes, and reduce overall hospitalization and rehabilitation time.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610331
Entities
People
- Cathy Rasmussen
Organizations
- Stratatech Corporation
- United States Army