Ahmed, Nehleen A Systematic Review of the Efficacy of Gene Therapy for Diabetes and Diabetes-Related Complications. 2022. Radford University, Doctoral Capstone Project. Radford University Scholars' Repository.
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Abstract
Objectives: Diabetes is a chronic condition characterized by excess blood sugar in genetically predisposed individuals. It is one of the top ten 10 causes of mortality and the top six causes of morbidity. The number of diabetes cases has tripled over the last 20 years and is projected to increase another 51% by 2045. It is evident that current methods of diabetes treatment have failed to stop this global crisis. Researchers are now pursuing gene therapy to find more effective treatments for diabetes. Numerous systematic reviews addressed the efficacy of pharmaceutical agents for treating diabetes in humans. However, no systematic review on the effectiveness of gene therapy for diabetes in humans was found. The purpose of this project was to conduct a systematic review to address this gap in the literature and determine whether gene therapy is an effective diabetes treatment. Methodology: The conventional steps of a systematic review were followed for this project. First, the PICO format was used to formulate focused review questions and define the inclusion and exclusion criteria. Then, an iterative search strategy was utilized to find peer-reviewed journal articles and grey literature from ten preselected databases. Articles were selected based on predetermined inclusion and exclusion criteria. The selection process was reported using a PRISMA flow chart. A kappa calculation was conducted to determine the inter-rater reliability of the selection process, and the quality of the selected studies was assessed using a Jadad scale. The selected studies were divided into sections by type of diabetes and related complications, then subsections based on the gene therapy pathways utilized in the studies and synthesized. Results: Forty-seven ongoing and completed trials were deemed suitable for inclusion in the systematic review. The kappa coefficient for the selection process was 0.93, indicating that interrater agreement was almost perfect. The median Jadad score was 4 with an interquartile range of 4, suggesting that the included studies were of high quality and had a low risk of bias. Fourteen out of the 16 completed trials with gene therapy for type 1 diabetes, four out of the five completed trials for type 2 diabetes, and 12 out of 15 completed studies on diabetes-related complications yielded positive results. Conclusions: This project addressed the gap in the literature by conducting a systematic review of 47 clinical trials on gene therapy for diabetes in humans. For type 1 diabetes, gene therapy trials to induce self-tolerance via T regulatory cells, interleukin cells, dendritic cells, genetically modified proinsulin, and monoclonal antibodies were particularly effective. For type 2 diabetes, gene therapy with glucokinase activators to increase insulin production and mesenchymal cell therapy to repair damaged beta cells demonstrated the most success. Gene therapy with growth factors successfully induced angiogenesis and treated diabetic neuropathy and critical limb ischemia. Gene therapy to inhibit vascular endothelial growth factors worked to treat diabetic vascular eye disorders. Overall, the gene therapy studies in this systematic review provided evidence that gene therapy is an effective treatment for treating type 1 and 2 diabetes and diabetes-related complications.
| Item Type: | Doctoral Capstone Project |
|---|---|
| Uncontrolled Keywords: | systematic review, gene therapy, diabetes, human, clinical trial |
| Subjects: | A General Works > AC Collections. Series. Collected works A General Works > AI Indexes (General) Q Science > Q Science (General) R Medicine > R Medicine (General) |
| Divisions: | Radford University > Waldron College of Health and Human Services > Health Sciences Program |
| Date Deposited: | 19 Apr 2023 16:48 |
| Last Modified: | 17 May 2023 00:50 |
| URI: | http://wagner.radford.edu/id/eprint/959 |
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