Lomitapide and Mipomersen-Inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 Synthesis

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art_BLOM_Lomitapide_and_MipomersenInhibiting_Microsomal_Triglyceride_Transfer_Protein_MTP_2019.PDF.pdf (401.73 KB)
Citações na Scopus
42
Tipo de produção
article
Data de publicação
2019
Editora
CURRENT MEDICINE GROUP
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
BLOM, Dirk J.
RAAL, Frederick J.
MARAIS, A. David
Autor de Grupo de pesquisa
Editores
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Organizadores
Citação
CURRENT ATHEROSCLEROSIS REPORTS, v.21, n.12, article ID 48, 10p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Purpose of Review The goal of this review is to evaluate the role of inhibiting the synthesis of lipoproteins when there is no or little residual LDL-receptor function as in patients with homozygous familial hypercholesterolaemia. Lomitapide is administered orally once a day while mipomersen is given by subcutaneous injection once a week. Lomitapide inhibits microsomal triglyceride transfer protein while mipomersen is an antisense oligonucleotide directed against apoB100. Recent Findings The pivotal registration trials for lomitapide and mipomersen were published in 2013 and 2010, respectively. More recently published data from extension trials and cohort studies provides additional information on long-term safety and efficacy. The mean LDL cholesterol reduction was 50% with lomitapide in its single-arm open-label registration trial. Mipomersen reduced LDL cholesterol by approximately 25% in its double-blind, placebo-controlled registration study. Both lomitapide and mipomersen therapy are associated with variable increases in hepatic fat content. The long-term safety of increased hepatic fat content in patients receiving these therapies is uncertain and requires further study. Both drugs may cause elevated transaminase in some patients, but no cases of severe liver injury have been reported. Lomitapide may also cause gastrointestinal discomfort and diarrhoea, especially if patients consume high-fat meals and patients are advised to follow a low-fat diet supplemented with essential fatty acids and fat-soluble vitamins. Mipomersen may cause injection-site and influenza-like reactions. The effect of lomitapide and mipomersen on cardiovascular outcomes has not been studied, but circumstantial evidence suggests that the LDL cholesterol lowering achieved with these two agents may reduce cardiovascular event rates.
Palavras-chave
Homozygous, Familial hypercholesterolaemia, Microsomal triglyceride transfer protein, Lomitapide, Mipomersen
URI
https://observatorio.fm.usp.br/handle/OPI/35416
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - ODS/03