Insulin gene therapy

Thule, P. M. and Liu, J. M. (2000). Regulated hepatic insulin gene therapy of STZ-diabetic rats. Gene Ther. 7, 1744—1752. 

Insulin-dependent diabetes mellitus (IDDM) is an example of a metabolic disease under active consideration for inducible gene therapy strategies. In this disorder, inflammatory cytokines have been shown to activate apoptosis in pancreatic beta cells. Experimental studies indicate that expression of insulinlike growth factor-1 (IGF-1) can prevent the cytokine-mediated destruction of beta cells of the pancreas (Giannoukakis et al., 2001). Regulated expression of IGF-1 in human pancreatic islets, to preserve beta cell function, may be a useful approach in the treatment of certain types of diabetes (Demeterco and Levine, 2001). 

This approach was effective in that it expressed IL-4 pancreas specifically, without any side-effects from the systemic expression of IL-4. These results also indicated that autoim-mune diabetes in NOD mice is not a systemic disease, and it can be modulated from the islet compartment. Therefore, for somatic gene therapy, the rat insulin pro-moter was inserted upstream of the IL-4cDNA (Lee et al., 2001a). This plasmid, pRIP-mIL-4 was complexed with water soluble lipopolymer and transfected in vitro. The results indicated that pRIP-mIL-4 expressed IL-4 cell-type specifically. 

The ability to transfer genes into islets and perhaps the insulin producing fl cells appears to represent an excellent opportunity to utilize gene therapy for improving the clinical efficacy of islet cell transplantation. Unlike the case of other organ transplants... 

Progress in insulin replacement strategies utilizing gene therapy... 

Kolodka, T. M., Finegold, M., Moss, L. and Woo, S. L. (1995). Gene therapy for diabetes mellitus in rats by hepatic expression of insulin. Proc. Natl. Acad. Sci. USA 92, 3293-3297. 

Gene Therapy Insufficient production of insulin in the body is often caused by deficiencies in the genes of the patient. If these genes could be replaced, the sickness could be cured. The technique is being tried out in the lab, but so far with little success. 

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