To date no biological treatment options specifically targeting the proteolytic nature of chronic wounds have been developed and marketed. Chronic skin wounds constitute an important medical problem for the growing aged population. 18% of diabetic patients over the age of 65 suffer from chronic, non-healing foot ulcers, and it is estimated that over 50,000 lower extremity amputations are due to diabetes in this same age group annually. 2.1 million Americans are diagnosed yearly with pressure ulcers, and the yearly incidence of venous ulcers is estimated to be 900,000. The creation of a cell-based gene therapy product with these properties would specifically target the needs of patients to reduce pain, risk of infection, and other complications thereby raising their quality of life. A persistent biochemical imbalance between proteinases and their inhibitors exists in the chronic wound bed. This imbalance may lead to abnormal degradation of the extracellular matrix, degradation of critical growth factors, and the breakdown of their respective cellular receptors within the wound environment further contributing to cellular dysfunction. Successful completion of Phase I milestones not only demonstrated the proof of principle that our human keratinocytes could be genetically modified to express and secrete bioactive proteinase inhibitor in monolayer culture, but identified a subset of clones to take into subsequent Phase II studies. The tissue evaluated in Phase II will mimic ExpressGraftTMShield, the engineered final product that will combat the excess proteolytic activity associated with chronic cutaneous wounds. Advances in ex vivo genetic engineering of a patented human keratinocyte cell line at Stratatech Corporation has made it uniquely positioned to complete this work. This Phase II study will 1) continue candidate clone screening in monolayer based on migration properties, as well as genomic integration, 2) examine their ability to form tissue that expresses a bioactive proteinase inhibitor, 3) perform preclinical animal efficacy studies, 4) identify the ideal candidate clone that will compose ExpressGraftTMShield, and 5) complete FDA-mandated safety testing. Successful completion of these milestones will expedite submission of an IND application to the FDA for initiation of a human clinical safety trial.
