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news.AVI BioPharma has announced encouraging preclinical data evaluating the use of antisense-based exon skipping pre-RNA interference technology, or ESPRIT, on the development of diabetes in a mouse model.
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The study demonstrated the effectiveness of AVI’s exon skipping technology in significantly delaying the onset of diabetes and in reversing the disease after onset. This work validates the application of ESPRIT technology in regulating the immune response in autoimmune diseases.
In the study, scientists modulated cytotoxic lymphocyte-associated antigen-4 (CTLA-4), a mediator in the development of diabetes, using ESPRIT compounds. The expected result was the prevention or alteration of the onset of diabetes in mice that are predisposed to developing diabetes (NOD mice).
In the first tests, mice were treated shortly after birth for 10 days with antisense to induce exon skipping. This short treatment delayed onset of diabetes by approximately 28 days compared to controls. In a second set of therapeutic experiments, adult mice with early signs of diabetes exhibiting elevated blood glucose levels were treated for 10 days with antisense exon skipping therapy. Over 50% of these animals were protected from full diabetes onset for the duration of the experiment (over 200 days). Both of these observations were statistically significant.
In addition to the primary data in these studies, AVI scientists intentionally triggered the opposite effect by inducing another altered splice form of CTLA-4 by employing a different antisense sequence. An enhanced immune activity was observed, leading to enhanced diabetic onset and severity. This may be relevant to medical situations where enhanced immune activity is desirable, such as in cancer or certain infections.
“ESPRIT technology can be used in two different disease settings,” said Dr Denis Burger, CEO of AVI. “This study demonstrated the impact of ESPRIT in interrupting an autoimmunity cascade, and we have previously shown that exon skipping can correct a genetic mutation in a muscular dystrophy model. We believe this study identifies a credible way to regulate the immune response in settings where T cells play a central role, as is the case in most autoimmune diseases.”