Exploring The Potential Of Gene Therapy For Patients With Diabetes
All of the above are considered in vivo gene therapy. In the diabetic foot wound, we also have experience using genetically engineered cells with Dermagraft (Advanced Biohealing) and Apligraf (Organogenesis), which are cultured ex vivo. If these cells were genetically modified prior to implantation, that would be ex vivo gene therapy.
A Closer Look At The Research On Gene Therapy For Podiatric Applications
Research has explored many different proteins in the healing cascade in regard to their potential benefits for diabetic ulcerations. Investigators have found that the topical application of insulin-like growth factors (IGF) I and II, and platelet derived growth factor (PDGF) in diabetic mice increased diabetic wound healing.7 Researchers have also shown that the use of transforming growth factor-alpha and fibroblast growth factor as monotherapies has shown promise in improving wound healing in diabetic mice.
In a study of intradermal injection of vascular endothelial growth factor A (VEGF-A), researchers showed promising results in mice with full thickness wounds by improving the wound healing rate while also inducing angiogenesis.8 While this technique was not on diabetic mice, researchers performed a similar study using the topical application of VEGF on mice and it showed parallel results.
In regard to targets of current gene therapy intervention, Tissue Repair Company is conducting a nationwide study using an adenovirus vector of topical gene active matrix (GAM) to transfer the PDGF gene into wound cells. 15 Research sponsored by the National Institutes of Health is looking at the intralesional injection of PDGF for venous leg ulcers. 15
VEGF is the target gene in several gene therapy trials for peripheral arterial disease and critical limb ischemia. Viromed is conducting a Phase I trial to evaluate the effect of injecting the VEGF gene intramuscularly.15 Sanofi-Aventis just completed a Phase II trial of VEGF for severe peripheral arterial disease in several European countries and it has now moved on to a Phase III trial in over 30 countries.15
Diabetic neuropathy is the target of two trials (Sangamo Biosciences and Caritas St. Elizabeth Hospital) evaluating the intramuscular injection of VEGF.15
Through proper delivery and therapeutic levels, gene therapy could provide intriguing benefits for the treatment of diabetic foot ulcers, diabetic neuropathy and peripheral arterial disease. In the event there are drastically impressive results in one or two gene therapy trials for these conditions, there would be a rapid acceptance and wide usage of this modality. It would behoove the podiatric physician to be familiar with the process of gene therapy and the disease targets currently under investigation.
Dr. Rogers is Director of the Amputation Prevention Center at Broadlawns Medical Center in Des Moines, Iowa. He directs research at the center and has been an investigator on over 20 clinical trials.
Ms. Lear is a third-year podiatric medical student at Des Moines University College of Podiatric Medicine and Surgery. She has conducted undergraduate research in gene identification and gene therapy.
Dr. Steinberg is an Assistant Professor in the Department of Plastic Surgery at the Georgetown University School of Medicine in Washington, D.C. He is a Fellow of the American College of Foot and Ankle Surgeons.
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