The need for effective treatment of chronic dermal wounds is poorly met, despite yearly medical costs exceeding $1 billion. Although growth factors are logical therapeutic candidates, for the most part they have not produced clinically significant benefits. A major limitation has been maintaining therapeutic levels at treatment sites. Delivering growth factor-encoding gene therapy vectors in biocompatible matrices, however, should allow for prolonged therapeutic production and retention in treated wounds. As platelet derived growth factor (PDGF)-B is particularly suited for wound treatment, we propose to utilize an adenoviral vector encoding this gene formulated in collagen as a wound therapeutic.
Specific Aim #1 will extend Phase I studies in order to select a final vector and collagen formulation, by measuring in vivo activity in an animal model.
Specific Aim #2 will perform preclinical efficacy, safety, and toxicology studies in preparation for human trials.
Specific Aim #3 will produce and test bulk virus for these trials. Finally, Specific Aim #4 will be a Phase I clinical study for the treatment of chronic diabetic ulcers. Successful completion of this work will then allow for progression to Phase II and III clinical studies, and commercialization of the final product.
Chronic dermal wounds are a significant public health concern, and yearly medical costs are estimated to exceed $1 billion. Presently, few therapeutic options allow for the augmentation of soft tissue repair, especially in patients with chronic ulcers. These studies will permit the development of novel therapeutics for wound treatment, as well as the initial evaluation of these products in human clinical trials. The combined use of gene therapy with a semi-solid matrix delivery system offers the possibility of delivering novel and potent therapeutic agents, with improved specificity and efficacy over that offered by existing treatments.
| Mulder, Gerit; Tallis, Arthur J; Marshall, V Tracy et al. (2009) Treatment of nonhealing diabetic foot ulcers with a platelet-derived growth factor gene-activated matrix (GAM501): results of a phase 1/2 trial. Wound Repair Regen 17:772-9 |
