MTP inhibition as a treatment for dyslipidaemias: time to deliver or empty promises?
- 17 January 2007
- journal article
- review article
- Published by Informa Healthcare in Emerging Therapeutic Targets
- Vol. 11 (2), 181-189
- https://doi.org/10.1517/14728222.11.2.181
Abstract
The development of cholesterol-lowering drugs, including a statins, bile acid sequestrants and cholesterol absorption inhibitors has expanded the options for cardiovascular prevention. Recent treatment guidelines emphasise that individuals at substantial risk for atherosclerotic coronary heart disease should meet defined lipid targets. Combination therapy with drugs that have different and complementary mechanisms of action is often needed to achieve these goals. Existing approaches to the treatment of hypercholesterolaemia are still ineffective in halting the progression of coronary artery disease in some patients despite combination therapies. Other patients are resistant to, or intolerant of, conventional pharmacotherapy and remain at high-risk of atherosclerotic cardiovascular disease, so that alternative approaches are needed. New agents, including inhibitors of microsomal triglyceride transfer protein (MTP), may play a future role, either alone or in combination, in the treatment of hyperlipidaemias. This review focuses on novel approaches to treat dyslipidaemias via the inhibition of MTP. Patients most suitable for use of MTP inhibitors include those with hepatic hypersecretion of apoB, including the metabolic syndrome, Type 2 diabetes mellitus and familial combined hyperlipidaemia, as well as homozygous and heterozygous familial hypercholesterolaemia. However, certain safety issues with these agents need resolving, particularly fatty liver disease.Keywords
This publication has 76 references indexed in Scilit:
- Apolipoproteins as markers and managers of coronary riskQJM: An International Journal of Medicine, 2006
- Recent studies of lipoprotein kinetics in the metabolic syndrome and related disordersCurrent Opinion in Lipidology, 2006
- Diabetic dyslipidaemia: from basic research to clinical practice*Diabetologia, 2003
- Apolipoproteins versus lipids as indices of coronary risk and as targets for statin treatmentThe Lancet, 2003
- Identification of Cysteine Pairs within the Amino-terminal 5% of Apolipoprotein B Essential for Hepatic Lipoprotein Assembly and SecretionPublished by Elsevier BV ,1997
- Apolipoprotein B Sequence Requirements for Hepatic Very Low Density Lipoprotein Assembly: EVIDENCE THAT HYDROPHOBIC SEQUENCES WITHIN APOLIPOPROTEIN B48 MEDIATE LIPID RECRUITMENTPublished by Elsevier BV ,1996
- The Amino Terminus of Apolipoprotein B Is Necessary but Not Sufficient for Microsomal Triglyceride Transfer Protein ResponsivenessPublished by Elsevier BV ,1996
- Recent progress in understanding apolipoprotein B.Circulation, 1990
- Apolipoprotein B-48 Is the Product of a Messenger RNA with an Organ-Specific In-Frame Stop CodonScience, 1987
- Complete protein sequence and identification of structural domains of human apolipoprotein BNature, 1986