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

Blom, Dirk; Raal, Frederick J.; Santos, Raúl D.; Marais, A. David

doi:10.1007/s11883-019-0809-3

Cited by 43 publications

(29 citation statements)

References 81 publications

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“…Mipomersen is an anti-sense oligonucleotide that is responsible for the degradation of mRNA translation in apolipoprotein B (APO-B). This drug inhibits the hepatic production of APO-B and reduces the assemblage of VLDL-C and other atherogenic lipoproteins [ 87 ]. Mipomersen is associated with an average reduction in LDL-C of 28% from baseline in addition to conventional therapy (e.g., maximum dose of statin) and is currently approved by the FDA for patients with HoFH and severe HeFH from the age of 12 years [ 64 , 87 ].…”

Section: Management Of Dyslipidaemia In Childrenmentioning

confidence: 99%

“…This drug inhibits the hepatic production of APO-B and reduces the assemblage of VLDL-C and other atherogenic lipoproteins [ 87 ]. Mipomersen is associated with an average reduction in LDL-C of 28% from baseline in addition to conventional therapy (e.g., maximum dose of statin) and is currently approved by the FDA for patients with HoFH and severe HeFH from the age of 12 years [ 64 , 87 ]. In children with HoFH, it was shown to be effective in reducing LDL-C but was poorly tolerated due to side effects, such as flu-like symptoms and reactions at the injection site [ 88 ].…”

Section: Management Of Dyslipidaemia In Childrenmentioning

confidence: 99%

“…On the other hand, lomitapide is a microsomal transfer protein of triglycerides (MTTP) inhibitor; given that MTTP mainly acts by binding TG to APO-B in the liver, lomitapide interferes with VLDL-C assembly and production [ 87 ]. Although adverse effects (e.g., gastrointestinal symptoms and fatty liver) occur frequently, lomitapide may lead to significant reductions in VLDL-C, LDL-C and TG by approximately 65%, 51% and 56%, respectively [ 89 ].…”

Section: Management Of Dyslipidaemia In Childrenmentioning

confidence: 99%

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Treatment of Dyslipidaemia in Children

Fiorentino

Chiarelli

2021

Biomedicines

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Childhood dyslipidaemia is one of the main traditional cardiovascular risk factors that initiate and exacerbate the atherosclerotic process. Healthcare providers may play a key role in the management of children with lipid abnormalities; however, they have to properly evaluate the normal lipid values and know the available treatment options in children and adolescents. Current guidelines recommend healthy behaviours as the first-line treatment for childhood dyslipidaemia. The therapeutic lifestyle changes should focus on dietary modifications, daily physical activity, reduction in body weight and tobacco smoking cessation. Parents play a key role in promoting their children’s healthy habits. In children with more severe forms of lipid abnormalities and in those who do not benefit from healthy behaviours, pharmacological therapy should be considered. Safe and effective medications are already available for children and adolescents. Statins represent the first-line pharmacological option, while ezetimibe and bile acid sequestrants are usually used as second-line drugs. Despite their limited use in children, other lipid-lowering agents (already approved for adults) are currently available or under study for certain categories of paediatric patients (e.g., familial hypercholesterolemia). Further studies are needed to evaluate the long-term efficacy, safety and tolerability of novel lipid-lowering drugs, especially in children.

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Section: Management Of Dyslipidaemia In Childrenmentioning

confidence: 99%

Section: Management Of Dyslipidaemia In Childrenmentioning

confidence: 99%

Section: Management Of Dyslipidaemia In Childrenmentioning

confidence: 99%

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Treatment of Dyslipidaemia in Children

Fiorentino

Chiarelli

2021

Biomedicines

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“…In FH heterozygous subjects with CHD on maximum tolerated dose of statins, mipomersen reduced LDL-C by −28%, lipoprotein (a) [Lp (a)] by −21%, and APOB of −26%. Side effects are frequent and include reactions to the injection site and flu-like symptoms [ 54 ]. Lomitapide inhibits the microsomal transfer protein of triglycerides (MTP), interfering in hepatic assembly and secretion of very-low-density lipoprotein (VLDL), since this protein is critical for transfer of triglycerides (TG) on APOB.…”

Section: Management Of Homozygous Fhmentioning

confidence: 99%

Current Approach to the Diagnosis and Treatment of Heterozygote and Homozygous FH Children and Adolescents

Cohen

Stefanutti²

2021

Curr Atheroscler Rep

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Purpose of Review To elucidate the current approach of care in pediatric patients with familial hypercholesterolemia (FH). We sought an answer to the question whether the advances and major changes in lipid management are relevant and apply to children and adolescents. Recent Findings Latest research findings clearly demonstrate that lowering cholesterol levels at a young age prevents vascular atherosclerotic changes and decreases cardiovascular events in adulthood and emphasizes the importance of early detection and intervention in the pediatric FH patients group. Summary FH is a common genetic disease caused by mutations in genes associated with the metabolism of low-density lipoproteins (LDL). The hallmark of FH is elevated LDL cholesterol (LDL-C) levels from birth and premature atherosclerotic cardiovascular disease (ASCVD). Often FH is either undiagnosed or diagnosed with a considerable delay, leading to vascular atherosclerotic changes and cardiovascular disease. Prompt identification of FH subjects is essential, to initiate early preventive measures. Safe and efficient pharmacological agents are approved for use in children and adolescents. Statins are the first line of therapy, in combination of ezetimibe. Unfortunately, these drugs do not warrant the achievement of therapeutic target, especially in HoFH patient. In the latter, lipoprotein apheresis (LA), which has been shown to be safe and effective, is strongly recommended. Finally, the new drugs still under study will allow a multimodal customized treatment. Lowering cholesterol levels at a young age hinders vascular atherosclerotic changes decreasing cardiovascular events in adulthood. Therefore, early detection, diagnosis, and intervention in FH patients are priority objectives.

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“…Mipomersen is an antisense oligonucleotide that inhibits the production of apoB-100 and lowers LDL-C by approximately 37%. Both represent new therapeutic approaches for patients with homozygous FH who do not reach LDL targets with statins [33].…”

Section: Lipid-lowering Drugsmentioning

confidence: 99%

Egyptian practical guidance in lipid management 2020

et al. 2021

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Background Numerous epidemiological investigations and randomized clinical studies have determined that dyslipidemia is a major contributor to atherosclerotic cardiovascular disease (ASCVD). Consequently, the management of serum cholesterol and low-density lipoprotein levels has become a central objective in the effort to prevent cardiovascular events. Main body Many guidelines were issued by different organizations and societies to define patient risk and establish important recommendations for management strategies. Newer cholesterol-lowering agents (non-statin drugs) are described, and their use is directed primarily to secondary prevention in patients at very high risk of new ASCVD. Conclusion The present guidance summarizes the current methods for risk estimation and outlines the most recent data on lipid management in a simple user-friendly format, to improve physician awareness and help implement guidelines in the daily practice.

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

Cited by 43 publications

References 81 publications

Treatment of Dyslipidaemia in Children

Treatment of Dyslipidaemia in Children

Current Approach to the Diagnosis and Treatment of Heterozygote and Homozygous FH Children and Adolescents

Egyptian practical guidance in lipid management 2020

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