Document Detail


Apolipoprotein B synthesis inhibition: results from clinical trials.
MedLine Citation:
PMID:  20508521     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Mipomersen is a second-generation antisense oligonucleotide developed to inhibit the synthesis of apolipoprotein B-100 in the liver. In this review we will summarize the results of recent preclinical and clinical studies addressing safety and low-density lipoprotein-cholesterol (LDL-c) lowering efficacy of this new compound. RECENT FINDINGS: In phase 3 clinical trials, mipomersen has been shown to significantly reduce LDL-c in patients with homozygous and heterozygous familial hypercholesterolemia on maximally tolerated lipid-lowering therapy. Injection site reactions, flu-like symptoms and increases in liver transaminases were the main adverse events. A recent safety study, designed to investigate the effects of mipomersen on intrahepatic triglyceride content, failed to show evidence of clinically relevant hepatic steatosis after 13 weeks of treatment. SUMMARY: Mipomersen is a new agent to lower LDL-c in patients at increased risk of cardiovascular disease and/or intolerant to statins. Whereas safety concerns have focused on hepatic fat accumulation, to date no evidence of clinically relevant increases of intrahepatic triglyceride content are reported. Ongoing and future studies are eagerly awaited to assess the impact of mipomersen on hepatic triglyceride content after prolonged exposure.
Authors:
Maartje E Visser; John J P Kastelein; Erik S G Stroes
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current opinion in lipidology     Volume:  21     ISSN:  1473-6535     ISO Abbreviation:  Curr. Opin. Lipidol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-13     Completed Date:  2010-10-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010000     Medline TA:  Curr Opin Lipidol     Country:  England    
Other Details:
Languages:  eng     Pagination:  319-23     Citation Subset:  IM    
Affiliation:
Department of Vascular Medicine, Academic Medical Center Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoproteins B / biosynthesis*,  metabolism
Clinical Trials as Topic
Drug Toxicity
Humans
Oligonucleotides / adverse effects,  pharmacology
Protein Biosynthesis / drug effects*
Chemical
Reg. No./Substance:
0/Apolipoproteins B; 0/ISIS 301012; 0/Oligonucleotides

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