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Amsterdam Molecular Therapeutics Successfully Lowers Cholesterol In Vivo With Enhanced Novel MicroRNA AAV Gene Therapy
Date:10/25/2010

siRNA sequences into microRNA scaffolds to silence Apolipoprotein B100 (AAV-miApoB) was able to significantly lower plasma cholesterol levels in vivo over a period of 18 weeks. These preliminary results suggest that this approach could lead to a treatment for high cholesterol in humans.

"Successful hepatocyte-specific delivery of microRNA (miRNA) and significant demonstration of gene silencing again illustrates the strength of AMT's AAV platform. We announced previously success with our short hairpin RNA targeting ApoB (shApoB) gene product but our newest data suggests our miRNA product is proving to be even better and safer," stated Jorn Aldag, CEO of AMT. "Certainly of the two approaches, the natural characteristics of miRNA, such as prolonged stable long term expression, undetectable toxicity profile, tissue specificity, as well as the significant efficacy, suggest a more favorable route to a viable treatment for high cholesterol. This future application of our technology may circumvent some of the delivery issues with the RNA approach. We intend to seek partners to exploit the full AAV technology potential in the RNA field."

Using its proprietary adeno-associated viral vectors (AAV), a single injection of AAV-miApoB transduced murine hepatocytes almost entirely and resulted in a reduction of total plasma cholesterol of 60-80% for an 18 week period. AAV delivery of miRNA, expressed from a liver-specific promoter, constitutes the second powerful approach by which AMT has demonstrated to lower plasma cholesterol, together with AMT's AAV shApoB gene therapy product tested in the same model of the disease. In our new approach, we went one step further and limited the expression of the inhibitory miApoB molecule only to the hepatocytes, which provides a higher safety profile, a feature very important for future clinical applications. Data were presented at the Hepatocyte User Group and Medicon Valley Hepatocyte User Forum (22-23 October) in Montpellier
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SOURCE Amsterdam Molecular Therapeutics B.V
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