Antisense oligonucleotides as therapeutics for hyperlipidaemias.
Hyperlipidaemia, due to elevations of low-density lipoprotein cholesterol (LDL-C) or triglycerides (TGs), is recognised as a significant risk factor contributing to the development of coronary heart disease (CHD), the leading cause of morbidity and mortality in the Western world. Even though a variety of established antihyperlipidaemic agents are available, the majority of high-risk patients do not reach their lipid goals, indicating the need for new and more effective therapeutics to be used alone or as combination agents with existing drugs. Antisense oligonucleotides (ASOs), designed to specifically and selectively inhibit novel targets involved in cholesterol/TG homeostasis, represent a new class of agents that may prove beneficial for the treatment of hyperlipidaemias resulting from various genetic, metabolic or behavioural factors. This article describes the antisense technology platform, highlights the advantages of these novel drugs for the treatment of hyperlipidaemia and reviews the current research in this area.
Crooke
Rosanne M
RM
Isis Pharmaceuticals, Inc., 1896 Rutherford Avenue, Carlsbad, CA 92008, USA. rcrooke@isisph.com
D000818:Animals; D053299:Apolipoprotein B-100; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism; D001056:Apolipoproteins C / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics / Q000627:therapeutic use*; D034622:RNA Interference; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000187:drug effects
D053299:Apolipoprotein B-100; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D034741:RNA, Small Interfering