71. Alpha 1 Antitrypsin (AAT) Gene Therapy for the Prevention of Type 1 Diabetes
Year: 2006
Type: article
Abstract: Type 1 diabetes is an autoimmune disease that results in the destruction of insulin producing b cells in the pancreatic islets. Although multiple factors contribute to this disease, an imbalance of the immune regulatory pathways plays an important role in the development of type 1 diabetes. Therefore, immunoregulatory and anti-inflammatory strategies hold great potential for the prevention of this autoimmune disease. Alpha 1 antitrypsin (AAT) is a serine proteinase inhibitor and exhibits various anti-inflammatory effects and protects against tissue damage or injury. In order to test the feasibility of AAT gene therapy for the prevention of type 1 diabetes, we have conducted a serial of experiments using rAAV vectors (serotype 1 and 2) for muscle gene delivery in non-obese diabetes (NOD) mouse model. Results from these studies showed that AAT gene therapy, contrary to control vector (expressing elafin) and saline, decreased insulitis, reduced the levels of autoantibody and prevented type 1 diabetes efficiently and in dose-dependent manner. T cell receptor spectratyping indicated that AAT gene therapy altered T cell repertoire diversity in splenocytes from NOD mice. Adoptive transfer experiments demonstrated that AAT gene therapy attenuated cellular immunity associated with beta cell destruction. Our results also showed that AAT protected islet cells against apoptosis and block cytotoxicity of NK cells. In summary, these data clearly demonstrate that AAT gene therapy efficiently prevented type 1 diabetes development in NOD mice and suggest a potential clinical application of this approach for type 1 diabetes prevention. In addition, that AAT gene therapy attenuates an autoimmune condition supports further investigations for application to other autoimmune disorders.
Source: Molecular Therapy
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W2074885204