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Therapeutic strategies for Type 1 and Type 2 diabetes mellitus
N Giannoukakis1, M Pietropaolo, M Trucco
1Dept of Pathology, and Diabetes Institute, University of Pittsburgh School of Medicine, Rangos Research Center, PA 15213, USA. ngiann1@pitt.edu
Abstract:
Although diabetes mellitus is a manageable disorder, the associated complications that result in significant morbidity and mortality worldwide necessitate novel approaches of pharmacologic, cell, and gene therapy for an eventual cure. A significant number of animal studies have demonstrated the potential of restoring normoglycemia by islet transplantation in the context of immunoregulation achieved by gene transfer of immunoregulatory genes to allo- and xenogeneic islets ex vivo. Examples include viral vector-mediated gene transfer of immunosuppressive cytokines, proteins that block co-stimulation and molecules that prevent apoptotic cell death. Additionally, gene and cell therapy has also been used to induce tolerance to auto- and alloantigens and to generate the tolerant state in autoimmune rodent animal models of Type 1 diabetes mellitus (T1DM) or rodent recipients of allogeneic/xenogeneic islet transplants. Gene transfer of putative autoantigens is one example. The achievements of gene and cell therapy in Type 2 diabetes mellitus (T2DM) are less evident, but seminal studies promise that this modality can be relevant to treat and perhaps prevent the underlying causes of the disease including obesity and insulin resistance. Herein, we present an overview of the current status of drug, gene and cell therapy for T1DM and T2DM and we propose novel therapeutic options that could be clinically useful.
Insights
Novel drug, cell, and gene therapies show promise for managing diabetes mellitus complications. Research explores islet transplantation with gene transfer for Type 1 diabetes and potential treatments for Type 2 diabetes, including obesity and insulin resistance.
Area of Science:
- Endocrinology and Metabolic Diseases
- Immunology
- Regenerative Medicine
Background:
- Diabetes mellitus presents significant global morbidity and mortality due to complications.
- Current management requires novel pharmacologic, cell, and gene therapies for a potential cure.
- Islet transplantation with immunomodulation offers a promising avenue for restoring normoglycemia.
Purpose of the Study:
- To review current drug, gene, and cell therapy approaches for Type 1 and Type 2 diabetes mellitus.
- To explore novel therapeutic options for clinical application.
- To highlight advancements in islet transplantation and immunomodulation.
Main Methods:
- Review of animal studies on gene transfer to islets for immunoregulation (e.g., immunosuppressive cytokines, co-stimulation blockers, anti-apoptotic molecules).
- Analysis of gene and cell therapy applications in inducing tolerance for autoimmune diabetes models and transplant recipients.
- Examination of emerging gene and cell therapy strategies for Type 2 diabetes, focusing on obesity and insulin resistance.
Main Results:
- Gene transfer to islets has shown potential in animal models for restoring normoglycemia and inducing tolerance.
- Viral vector-mediated gene transfer has been used to deliver immunomodulatory genes to islets.
- Cell and gene therapies are being investigated to induce tolerance to auto- and alloantigens in diabetes models.
Conclusions:
- Drug, cell, and gene therapies offer promising avenues for treating diabetes mellitus and its complications.
- Islet transplantation combined with gene-mediated immunomodulation is a key strategy for Type 1 diabetes.
- Further research in gene and cell therapy holds potential for treating Type 2 diabetes and its underlying causes like obesity and insulin resistance.