Journal
JOURNAL OF CLINICAL LIPIDOLOGY
Volume 4, Issue 5, Pages 350-356Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacl.2010.08.015
Keywords
Antisense oligonucleotide; Apolipoprotein B; Familial hypercholesterolemia; LDL cholesterol; MTP inhibitor; Thyroid hormone analogue
Categories
Funding
- Merck
- ISIS/Genzyme
- Abbott
- Aegerion
- Novartis
- Glaxo-Smith-Kline
- Amarin
- Takeda
- Sanofi-Aventis
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Patients with familial hypercholesterolemia (FH) are not always able to achieve target levels of low-density lipoprotein (LDL) cholesterol with currently available medications. A number of novel pharmaceutical approaches to LDL cholesterol-lowering have been in development. Antisense oligonucleotides are molecules that are injected subcutaneously and cause decreased release of apolipoprotein B-containing lipoproteins from the liver. Microsomal transfer protein inhibitors block the accumulation of triglyceride into apolipoprotein B precursors. Squalene synthase inhibitors partially block a late step in cholesterol biosynthesis. Proprotein convertase subtilisin kexin type 9 inhibitors can lead to increased LDL cholesterol receptor functioning and thereby decrease LDL cholesterol levels. Thyroid hormone analogues lower LDL cholesterol and other lipoproteins by a selective effect on certain thyroid hormone receptors, avoiding the adverse effects of excessive thyroid hormone levels. Several of these classes of lipid-modifying agents are currently in clinical trials. Long-term safety data will be needed before any are available to be used clinically, but some hold significant potential for improving treatment options for patients with FH. (C) 2010 Published by Elsevier Inc on behalf of the National Lipid Association.
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