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Antisense Oligonucleotides for the Treatment of Dyslipidemia.
MedLine Citation:
PMID:  21418033     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
New studies further demonstrate that lowering low-density lipoprotein (LDL)-cholesterol, at least with the use of statins, decreases the risk of cardiovascular disease (CVD). Subsequently national and international guidelines have set target levels for LDL-cholesterol that are progressively lower, making the likelihood of patients attaining them progressively more limited, even with the use of all currently available medications. Thus, there is a clear need for new therapeutic approaches to lower LDL-cholesterol. Antisense oligonucleotides (ASO) represent a new paradigm for the discovery of potentially powerful and selective drugs with a mechanism of action based on the concept of base-pair hybridizazion as described by Watson and Crick, resulting in decreased production of target proteins. In mouse and human genetic models it has been shown that decreasing hepatic apolipoprotein B-100 (ApoB-100) as well as proprotein convertase subtilisin-like/kexin type 9 (PCSK9) production is associated with lower circulating LDL-cholesterol levels. Purpose of this review is to discuss the available data on the effects of various ASO used for the treatment of dyslipidemia, with the main focus on ASO against ApoB-100, the most advanced in clinical development, and on PCSK9.
Authors:
I Gouni-Berthold; H K Berthold
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-22
Journal Detail:
Title:  Current pharmaceutical design     Volume:  -     ISSN:  1873-4286     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9602487     Medline TA:  Curr Pharm Des     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Internal Medicine II, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany. ioanna.berthold@uni-koeln.de.
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