Exploring The Potential Of Gene Therapy For Patients With Diabetes

By Lee C. Rogers, DPM, and Elisa Lear, BS

   Gene therapy has entered the forefront of medicine and there may be potential benefits in all fields of healthcare. The potential for gene therapy to target disease has vastly expanded since the first successful human treatment for severe combined immune deficiency (SCID) emerged in 1990.

   In podiatric medicine, one proposed target that has devastating consequences is the diabetic foot ulcer. As diabetes mellitus continues to become more common within the podiatric population, the necessity to care for wounds and focus on limb preservation is becoming more essential.

   Currently, there are nearly 24 million people who have diabetes mellitus in the United States. Accordingly, nearly 8 percent of the country’s population has diabetes.1 Diabetes not only plagues the geriatric community but the youth of our country. There are a multitude of complications that accompany this disease and podiatric physicians are on the frontline since diabetic foot exams and foot care programs can decrease amputation by 45 to 85 percent.2

   There is a whirlwind of research around genetically modified proteins and viruses, and their potential benefits in helping to facilitate healing for diabetic foot ulcers. As the research continues on diabetic wounds, it is also becoming more clear that these wounds have altered blood flow, impairments with fighting microbial pathogens and abnormal chemokine expression, resulting in abnormal inflammatory responses.3

   The healing process is very complex and there are a series of steps and certain components that need to be in place to ensure proper wound healing. To this end, Martin, et al., discussed the basic steps of inflammation, the formation of granulation tissue, angiogenesis and tissue remodeling.4 When looking at the gene expression in wound healing and the cascade of components that are necessary at certain moments in time to heal wounds, if one of those components is not present, it could delay the whole process.5

   A comparison study of diabetic mice versus non-diabetic mice showed that pertinent components necessary for healing, such as IGF-I and IGF-II mRNA, were delayed in expression for the diabetic mice.6-9 There has been a wide range of research centering on the idea that diabetic wounds express menial levels or potentially fail to express some of the necessary components for healing. In the effort to aid in wound healing for those with diabetes, multiple research studies have looked at engineering these components that could be potentially lacking, delivering them to the vicinity of the wound whether it is via topical application or injection.6-9

A Pertinent Overview Of Gene Therapy

   Gene therapy is defined as “treatment of a disease by introducing a new gene into a cell.” 10 One can apply gene therapy to virtually any field of medicine. A gene is a sequence of DNA that “codes” for a certain cell function. The simplest building block of the gene is the nucleotide, which is comprised of DNA. Several genes make up a chromosome. All the chromosomes together constitute the human genome. There are approximately 25,000 genes in each human cell. The Human Genome Project identified nearly all the genes, although their functions have not been clearly defined. 11

   One of the more challenging aspects to gene therapy is how to deliver the gene into the host cell. Different vectors can accomplish gene delivery. Transfer of naked DNA on plasmids (double-stranded DNA) has proven inefficient. Initial transfers used a retrovirus (single-stranded RNA) to replace the faulty gene. Adenovirus (double-stranded DNA) vectors have been in use but these vectors are not incorporated into the human genome, resulting in seemingly transient effects. 11 Accordingly, the properties of adenoviruses seem more suited to use in diabetic foot ulcers, in which a transient effect is necessary to heal the wound.

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