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

, France, and at the European Society for Gene and Cell Therapy Annual Conference (22-25 October) in Milan, Italy.

In the new study, mice received intra-venous injections with equal doses of 1011 gc per animal AAV-shApoB or AAV-miApoB and were examined for 18 weeks. Expression of the shApoB and miApoB resulted in 90% ApoB protein knock-down, associated with 80% cholesterol decrease in murine plasma for the first 6 weeks. However, after 8 weeks the effect of the shApoB started to wear off, while miApoB remained effective in ApoB and cholesterol reduction for up to 18 weeks. Ongoing research aims to determine the mechanism for the differences seen between long-term AAV-shApoB and AAV-miApoB efficacy in murine livers. We believe that the long-term stability of the miApoB is due to its lower toxicity and off-target properties compared to shApoB because expression of miApoB is specifically limited to hepatocytes.

ApoB100 is the structural protein of Low Density Lipoprotein (LDL) particles that carry cholesterol. Silencing the activity of ApoB100 with miRNA or shRNA lowers plasma LDL-cholesterol by 60-80% and has the potential to be used to treat hypercholesterolemia and associated cardiovascular disease.

About Amsterdam Molecular Therapeutics

AMT is a leader in the development of human gene based therapies. Using adeno-associated viral (AAV) derived vectors as the delivery vehicle of choice for therapeutic genes, the company has been able to design and validate what is probably the first stable and scalable AAV production platform. This proprietary platform can be applied to a large number of rare (orphan) diseases that are caused by one faulty gene. Currently, AMT has a product pipeline with several AAV-based gene therapy products in LPLD, Hemophilia B, Duchenne Muscular Dystrophy, Acute Intermittent Porphyria, and Parkinson's Disease at different stages of research or development. AMT was founded in 1998 and is based in Amsterdam.

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