Microsomal Transfer Protein Inhibitor Research Articles

Contemporary hypolipemic therapy: possibilities of novel hypolipemic drugs in correction of lipid metabolism disorders. Review

Dyslipidemia plays a role of significant risk factor for development and progression of cardiovascular diseases. Today several classes of hypolipemic drugs with evidenced effectiveness are used. But some patients don’t tolerate medicines with high efficacy or can’t achieve the targeted blood lipid profile levels even in case of the use of maximal doses or combined therapy. This necessitates the creation of new hypolipidemic agents.
 The review is devoted to discussion of new directions of influence on impaired lipid metabolism through creation of new classes of hypolipemic drugs with some perspectives of effective correction of lipid factors of cardiovascular risk (CVR) in cases of impossibility to achieve the targeted levels of low‑density lipoprotein cholesterol (LDL‑C) or there is a residual CVR caused by elevated serum triglyceride (TG) levels and/or low levels of high‑density lipoprotein cholesterol (HDL‑C).
 Among the novel drugs for hypercholesterolemia (HCE) correction, considerations are given for some mechanisms of action and efficacy of application of proprotein convertase subtilisin‑kexine type 9 (PCSK9) inhibitors as well as bempedoic acid (adenosine triphosphate citrate lyase inhibitor) and inclisiran, a small synthesized interfering ribonucleic acid (RNA) with its ability to blockade genes‑regulators of hepatic PCSK9 activity. The novel agents for hypertriglyceridemia correction, discussed in the review, include icosapent ethyl (a high purified and firm ester of ethyl‑eicosapentoenic acid), pemafibrate (the first selective modulator of α‑receptors activated by peroxisome proliferator), apolipoprotein C‑III (ApoC‑III) inhibitors (volasenorsen, olesarsen), mipomersen (antisense nucleotide for matrix RNA of apolipoprotein B‑100), lomitapide (inhibitor of microsomal TG transfer protein) and inhibitors of angiopoietin‑like protein 3 (ANGPTL3) (evinacumab, vupanorsen). Among the new approaches to HDL‑C elevation an attention is paid to the experimental and clinical investigations of recombinant HDL, agents with recombinant lecithin‑cholesterol‑acyl‑transferase (LCAT), and apolipoprotein A‑I (ApoA‑I) mimetic peptides. For the lowering of blood lipoprotein(a) (LP(a)) level the possibilities of pelacarsen, an antisense oligonucleotide for matrix RNA of apolipoprotein(a) (apo(a)) contained in LP(a) molecule and olpasiran, a small interfering RNA for LP(a) molecule inhibited apo(a) synthesis are uncovered. A high probability of clinical application in the nearest future will have novel drugs approved by US Food and Drug Administration (FDA) and European Medicines Agency (EMA) such as bempedoic acid and inclisiran for HCE correction as well as lomitapide for the treatment of familial HCE.

Regulating microsomal triglyceride transfer protein with natural products for the treatment of hyperlipidaemia

Hyperlipidaemia, characterised by elevated levels of lipids, particularly LDL-C, is a significant risk factor for atherosclerotic cardiovascular disease. While synthetic inhibitors of microsomal triglyceride transfer protein (MTP) have shown potential in lowering LDL-C, they are associated with adverse effects. This study explores a novel approach by screening natural products to identify plant extracts that down-regulate MTP gene expression, aiming to reduce hyperlipidaemia with fewer side effects. Modulating MTP expression, rather than direct inhibition, offers a promising avenue for lowering plasma lipids and mitigating cardiovascular risk. Various plant extracts were examined for their potential as MTP down-regulators, with Liquorice root and Pomegranate rind extracts demonstrating the highest efficacy. Additionally, the study assessed the total phenolic content of these extracts, revealing their ­antioxidant capacity. This research provides a foundation for further investigation into bioactive molecules as potential anti-hyperlipidemic agents with improved safety profiles, addressing a critical need in cardiovascular disease prevention.

Gene and cell therapy approaches for familial hypercholesterolemia: An update.

Familial hypercholesterolemia (FH) is a common autosomal codominant hereditary illness marked by the heightened risk of early atherosclerotic cardiovascular disease and high blood levels of low-density lipoprotein cholesterol (LDL-C). FH patients can have homozygous or heterozygous variants. This condition has been linked to variations in the genes for the LDL receptor (LDLR), apolipoprotein B, proprotein convertase subtilisin/Kexin 9 (PCSK9), and LDLR adaptor protein 1. Drugs such as statins, ezetimibe, and PCSK9 inhibitors are currently widely available, allowing for the theoretical normalization of plasma LDL-C levels mostly in patients with heterozygous FH. However, homozygous FH patients usually have a poor response to traditional lipid-lowering therapy and may have a poor prognosis at a young age. LDL apheresis and novel pharmacological therapies such as microsomal transfer protein inhibitors or anti-angiopoietin-like protein 3 monoclonal antibodies are extremely expensive and unavailable in most regions of the world. Therefore, the unmet need persists for these patients. In this review, we discuss the numerous gene delivery, gene editing, and stem cell manipulation techniques used in this study to correct FH-causing LDLR gene variations in vitro, ex vivo, and in vivo. Finally, we looked at a variety of studies that corrected genetic defects that caused FH using the ground-breaking clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology.

New Trends and Therapies for Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is associated with an elevated risk of atherosclerosis. The finding of monogenic defects indicates higher atherosclerotic risk in comparison with hypercholesterolemia of other etiologies. However, in heterozygous FH, cardiovascular risk is heterogeneous and depends not only on high cholesterol levels but also on the presence of other biomarkers and genes. The development of atherosclerosis risk scores specific for heterozygous FH and the use of subclinical coronary atherosclerosis imaging help with identifying higher-risk individuals who may benefit from further cholesterol lowering with PCSK9 inhibitors. There is no question about the extreme high risk in homozygous FH, and intensive LDL-cholesterol-lowering therapy must be started as soon as possible. These patients have gained life free of events in comparison with the past, but a high atherosclerosis residual risk persists. Furthermore, there is also the issue of aortic and supra-aortic valve disease development. Newer therapies such as inhibitors of microsomal transfer protein and angiopoietin-like protein 3 have opened the possibility of LDL-cholesterol normalization in homozygous FH and may provide an alternative to lipoprotein apheresis for these patients. Gene-based therapies may provide more definite solutions for lowering high LDL cholesterol and consequent atherosclerosis risk for people with FH.

Lomitapide in paediatric homozygous familial hypercholesterolemia – Real-world clinical experience from South Africa

Background and Aims : Homozygous familial hypercholesterolemia (HoFH) is a genetic disorder characterized by extremely high levels of circulating low-density lipoprotein cholesterol (LDL-C). Lomitapide is a microsomal transfer protein inhibitor that has demonstrated LDL receptor-independent lipid-lowering efficacy in HoFH patients in long-term clinical trials and real-world studies.

Dyslipidaemia - Current and Future Treatment Paradigm

Dyslipidaemia is one of the major risk factors for coronary vascular disorders. Dyslipidaemia prevention and management can have a great impact on cardiovascular morbidity and mortality. There are many lipid-modifying pharmacological medicines on the market, and more are being developed. New guidelines recommend aggressive lipid-lowering targets depending on the atherosclerotic cardiovascular (ASCVD) risk. Depending on the risk of these risks, new guidelines advocate aggressive lipidlowering targets. For many years, statins had been the standard care, and demonstrated to reduce the risk of cardiovascular events. Novel molecules such as PCSK9 inhibitors, selective inhibitors of microsomal triglyceride transfer protein, small interfering RNA (siRNA), and antisense oligonucleotide drugs, could be interesting new additions to effective lipid-lowering therapy, are now accessible. We look into the history, method of action, key clinical studies, and side effects of therapeutic targets for dyslipidaemia to see where they fit into the therapy armamentarium now and in the future.

Familial Hypercholesterolaemia: An Updated Overall Management

Familial hypercholesterolaemia (FH), the commonest and serious but potentially treatable form of inherited dyslipidaemias, is characterised by severely elevated plasma low-density lipoprotein-cholesterol (LDL-C) level, which subsequently leads to premature coronary artery disease (pCAD). Effectiveness of FH early detection and treatment is supported by the outcome of several international cohort studies. Optimal FH management relies on prescription of statins either alone or together with other lipid-lowering therapies (LLT). Intensive lifestyle intervention is required in parallel with LLT, which should be commenced at diagnosis in adults and childhood. Treatment with high intensity statin should be started as soon as possible. Combination with ezetimibe and/or bile acid sequestrants is indicated if target LDL-C is not achieved. For FH patients in the very-high risk category, if their LDL-C targets are not achieved, despite being on maximally tolerated statin dose and ezetimibe, proprotein convertase subtilisin/kexin type1 inhibitor (PCSK9i) is recommended. In statin intolerance, ezetimibe alone, or in combination with PCSK9i may be considered. Clinical evaluation of response to treatment and safety are recommended to be done about 4-6 weeks following initiation of treatment. Homozygous FH (HoFH) patients should be treated with maximally tolerated intensive LLT and, when available, with lipoprotein apheresis. This review highlights the overall management, and optimal treatment combinations in FH in adults and children, newer LLT including PCSK9i, microsomal transfer protein inhibitor, allele-specific oligonucleotide to ApoB100 and PCSK9 mRNA. Family cascade screening and/or screening of high-risk individuals, is the most cost-effective way of identifying FH cases and initiating early and adequate LLT.

Lomitapide for treatment of homozygous familial hypercholesterolemia: The Québec experience

Background and aimsHomozygous familial hypercholesterolemia (HoFH) is an orphan disease, most often caused by bi-allelic mutations of the LDLR gene. Patients with HoFH have elevated LDL-C levels >13 mmol/L, tendinous xanthomata and severe, premature atherosclerotic cardiovascular disease (ASCVD). Untreated, most HoFH patients die of ASCVD in youth. New therapeutic modalities include lomitapide, an inhibitor of microsomal triglyceride transfer protein that lowers hepatic LDL-C production. We have recently identified 79 Canadian patients with HoFH. Here, we describe our experience with lomitapide in the province of Quebec, a geographic area known to have a high prevalence of HoFH. MethodsThis is a retrospective case series of 12 HoFH patients followed at three lipidology centers in the province of Quebec. ResultsMean age of the patients was 44 ± 18 years; age at time of HoFH diagnosis ranged from 2 to 59 years. All patients were on a statin and ezetimibe 10 mg/day and five patients were treated with LDL apheresis. Treatment with lomitapide reduced LDL-C levels by 38% (intention-to-treat). Intolerable gastrointestinal side effects were observed in 3/12 patients and were the main reason for treatment discontinuation. Three patients tolerated lomitapide at doses ranging between 5 and 30 mg/day without major side effects. Downwards drug titration was necessary in the 6 remaining patients because of gastrointestinal side effects (n = 5) and elevated liver enzymes (n = 1), and 2 of them finally discontinued treatment. ConclusionsLomitapide may be used to further decrease LDL-C in HoFH patients; gastrointestinal side effects and hepatic toxicity may limit adherence.

Současné a budoucí trendy v léčbě dyslipidemií

Lipid-lowering treatment is a part of prevention and treatment of vascular diseases caused by atherosclerosis. We need new strategies for modifying plasma lipoprotein levels in the light of new findings that reduce target lipid levels further lower, as well as the growing population of patients for whom existing treatments cannot be offered. The spectrum of existing drugs (new statins) is widening, pharmacological treatments (recombinant lipoproteins-bound statins), improved forms of established drugs (selective PPARα receptor modulators) are coming. The new procedures include fixed combinations of established drugs improving adherence and intensifying lipid modifying effects (statin + ezetimibe). The portfolio of lipid-lowering therapies today also includes monoclonal antibodies against PCSK9 (PCSK9 inhibitors). The main direction of future development is biotechnology using the principle of so-called antisense therapy, i.e. the use of specific oligonucleotide sequences blocking the translation of the selected protein. These novel therapies targeting, for example, apolipoprotein B, apolipoprotein CIII, or lipoprotein(a) are in various stages of clinical trials. A simi-lar (but not identical) principle is the use of RNA silencing - interference with gene expression using short sequences of double-stranded RNA (e.g. inclisiran siRNA against PCSK9). Innovations in the field of hypolipidemic pharmacotherapy in our country may also be inhibitors of microsomal triglyceride transfer protein (approved for use in homozygotes for familial hypercholesterolemia and experimentally also for familial chylomicronemia). The small molecule ATP citrate lyase inhibitor, bempedoic acid, decreases LDL-C by a further 20 % over and above the reduction achievable by a statin. In a broader sense, the novelty of hypolipidemic pharmacotherapy includes treatment options for some rare metabolic diseases (eg. enzyme replacement therapy for acid lysosomal lipase deficiency) manifested by lipoprotein metabolism abnormalities. All these new directions must aim at the common main goal of reducing the incidence of cardiovascular and gastrointestinal complications of dyslipidemia. Clinical research also aims to prove these effects.

Case report: The efficacy and safety of lomitapide in a homozygous familial hypercholesterolemic child

We report for the first time the efficiency and safety of a 49-month compassionate use of the microsomal transfer protein inhibitor lomitapide in a child with homozygous familial hypercholesterolemia. On average, 20 mg of lomitapide caused a 37% reduction in low-density lipoprotein cholesterol levels on top of ezetimibe and atorvastatin. The drug was well tolerated with no changes in liver enzymes and occurrence of steatosis on hepatic ultrasound. The patient presented adequate growth and sexual maturation. Nonetheless, there was progression in either subclinical atherosclerotic carotid or aortic valve diseases. Further studies are necessary to test the impact and safety of lomitapide in children with homozygous familial hypercholesterolemia.

The effect of lomitapide on cardiovascular outcome measures in homozygous familial hypercholesterolemia: A modelling analysis.

Background Patients with homozygous familial hypercholesterolemia are at high risk of cardiovascular disease due to high low-density lipoprotein (LDL)-cholesterol levels. Cardiovascular disease outcome studies are impossible to conduct, due to the rarity of homozygous familial hypercholesterolemia. We modelled the potential efficacy of lomitapide, a microsomal transfer protein inhibitor, on major adverse cardiovascular events (MACEs) and survival. Design We calculated the effect on cardiovascular outcomes of a 38% plasma LDL-cholesterol reduction induced by lomitapide. Methods Age-dependent hazards and treatment-dependent hazard ratios for mortality and time to first MACE were calculated from an observational study of 149 South African homozygous familial hypercholesterolemia patients. Cardiovascular-related mortality hazards were derived by adjusting for general population non-cardiovascular-related mortality. For every mmol/L LDL-cholesterol reduction, a relative risk reductions of 23% (mortality) and 15% (major adverse cardiovascular events) were observed. Results For the most robust model, baseline median survival with current treatments (LDL-cholesterol 8.7 mmol/L) was 48 years. In the survival benefit analysis, starting lomitapide at age 18 years and reducing LDL-cholesterol by 3.3 mmol/L from baseline would increase life expectancy by 11.2 years and delay the time to first MACE by 5.7 years. Analysis suggested lifetime lomitapide treatment could increase median life expectancy by 11.7 years and time to first MACE by 6.7 years. Conclusion Our modelling analyses show that additional LDL-cholesterol lowering by lomitapide may increase life expectancy in patients with homozygous familial hypercholesterolemia. Further clinical studies are warranted to determine the cardiovascular morbidity and mortality benefits of lomitapide.

Lomitapide for the treatment of hypercholesterolemia

ABSTRACTIntroduction: Homozygous familial hypercholesterolemia (HoFH) is a serious rare inherited condition that leads to extremely elevated levels of low density lipoprotein cholesterol (LDL-C), and predisposes affected individuals to high risk of atherosclerotic vascular disease. Traditional therapies are largely ineffective in managing the hypercholesterolemia in these patients; diet and regular LDL-apheresis are the mainstays of management. Lomitapide is an inhibitor of microsomal triglyceride transfer protein (MTP) that blocks the assembly of metabolic precursors of LDL particles. Lomitapide has been approved for use in the HoFH population.Areas covered: This article explores the basic properties of lomitapide, including its pharmacodynamic, pharmacokinetic and metabolic profiles. It also reports the current market status of lomitapide and its close competitors. Trials of lomitapide are also briefly reviewed as well as the safety and tolerability of the drug.Expert opinion: Lomitapide has been recently approved for use in HoFH, a population that has been traditionally very difficult to effectively manage. While lomitapide has some safety concerns, including gastrointestinal symptoms and potential hepatotoxicity, and has yet to prove long term efficacy on hard cardiovascular endpoints, it does represent an attractive treatment option for a small group of patients who, until now, had very limited available effective therapies.

Achievement of European atherosclerosis society (EAS) targets with lomitapide, a microsomal transfer protein inhibitor in homozygous familial hypercholesterolaemia (HoFH)

Achievement of European atherosclerosis society (EAS) targets with lomitapide, a microsomal transfer protein inhibitor in homozygous familial hypercholesterolaemia (HoFH)

LOWER, a registry of lomitapide-treated patients with homozygous familial hypercholesterolemia: Rationale and design

Lomitapide is an orally active selective inhibitor of microsomal triglyceride transfer protein approved as adjunctive therapy for homozygous familial hypercholesterolemia (HoFH). The Lomitapide Observational Worldwide Evaluation Registry (LOWER) is a global, long-term, prospective, observational treatment registry established as a regulatory requirement. LOWER will evaluate the long-term safety and effectiveness of lomitapide in clinical practice. The objectives include evaluation of the occurrence of events of special interest and assessment of the long-term effectiveness of lomitapide in maintaining reduced serum lipid levels. LOWER is a noninterventional study open to eligible lomitapide-treated patients. At least 300 patients will be enrolled and followed for at least 10 years. Data will be collected in conjunction with usual care visits and analyzed annually. LOWER includes a cardiovascular imaging substudy; an independent pregnancy exposure registry is also open. Events of special interest include hepatic abnormalities, gastrointestinal events, certain gastrointestinal tumors, major adverse cardiovascular events, and events associated with coagulopathy. Data will be collected on demographics, diagnosis, patient history, lomitapide dosing, concomitant treatment, lipid profile, and other laboratory results. LOWER will assess the long-term safety, efficacy, and patterns of use of lomitapide, increase understanding of the benefit-to-risk profile, and add to knowledge of HoFH.

Novel therapeutics in hypertriglyceridemia.

We provide an overview of recent advances in the therapy of hypertriglyceridemia, focusing on several new therapies with potential for treating of familial chylomicronemia, other forms of hypertriglyceridemia, and for triglyceride-lowering in patients with other lipid disorders. Newer triglyceride-lowering modalities under evaluation include gene therapy for lipoprotein lipase deficiency (alipogene tiparvovec), and antisense oligonucleotides against mRNA for apolipoproteins B (mipomersen) and C3 (volanesorsen, ISIS 304801). Other potential therapies include small molecule inhibitors of microsomal triglyceride transfer protein (lomitapide) and diacylglycerol acyltransferase-1 (pradigastat), and a monoclonal antibody against angiopoietin-like protein 3 (REGN1500). There is also renewed interest in omega-3 fatty acids, and in developing potent and selective agonists of peroxisome proliferator-activated receptors. Several promising triglyceride-lowering therapies are at various stages of development; a few are even available in some markets. Although existing data suggest good biochemical efficacy, data on long-term clinical outcomes are still limited. For some therapies, cost will be an important consideration, and use will likely be restricted to orphan indications, for example very severe cases of hypertriglyceridemia as seen in familial chylomicronemia syndrome, although some therapies could theoretically be more broadly used one day for cardiovascular disease prevention.

Treatment of hypertriglyceridemia: a review of current options.

Hypertriglyceridemia is an important marker of increased levels of highly atherogenic remnant-like particles. The importance of lowering plasma levels of triglycerides (TG) has been called into question many times, but currently it is considered an integral part of residual cardiovascular risk reduction strategies. Lifestyle changes (improved diet and increased physical activity) are effective TG lowering measures. Pharmacological treatment usually starts with statins, although associated TG reductions are typically modest. Fibrates are currently the drugs of choice for hyperTG, frequently in combination with statins. Niacin and omega-3 fatty acids improve control of triglyceride levels when the above measures are inadequately effective. Some novel therapies including anti-sense oligonucleotides and inhibitors of microsomal triglyceride transfer protein have shown significant TG lowering efficacy. The current approach to the management of hypertriglyceridemia is based on lifestyle changes and, usually, drug combinations (statin and fibrate and/or omega-3 fatty acids or niacin).

Abstract 18509: Defining Renal Uptake of Circulating Lipids

A prominent histological feature of chronic kidney disease, including that due to diabetes, is the accumulation of neutral lipids in the nephron. However, existing research on kidney lipid metabolism is limited. Therefore we characterized lipid accumulation in mouse models. We hypothesized that the major source of lipids in the kidney is circulating triglyceride (TG)-rich lipoproteins brought into the cells of the kidney via the coordinated action of lipoprotein lipase (LPL) and cluster of differentiation 36 (CD36). To test this hypothesis, we fasted mice overnight and inhibited LPL and CD36. We did not observe a change in TG accumulation in the kidney when LPL action was blocked using with poloxmer 407. We then used a microsomal TG transfer protein inhibitor, which inhibits TG-rich lipoprotein assembly, to lower circulating TG-rich lipoproteins. Intracellular kidney TG did not decrease but in fact increased up to 40% in the fasted state after the inhibitor was given, mirroring what was seen in the liver. There was no difference in TG accumulation in the kidneys of fasted Cd36 -/- mice. Furthermore, we did not observe a change in uptake of radiolabeled oleic acid in the kidneys of these mice. Genes which regulate fatty acid oxidation or de novo lipogenesis were also unchanged in Cd36 -/- compared to Cd36 +/+ . Surprisingly, apoC-III deficiency increased renal uptake of a TG-emulsion, as had been found in the liver. Finally, we measured TG in kidneys from streptozotocin-treated and Akita diabetic mice without renal failure. Neither of these models accumulated higher amounts of TG compared to non-diabetic controls; however, Akita mice down regulated fatty acid oxidation genes and had twice the intracellular free fatty acids. These findings provide novel insight into the lipid biochemistry of the kidney, showing it differs from other high energy requiring peripheral organs such as heart.

JTT-130, a novel intestine-specific inhibitor of microsomal triglyceride transfer protein, ameliorates lipid metabolism and attenuates atherosclerosis in hyperlipidemic animal models

JTT-130 was developed as an intestine-specific MTP inhibitor designed to rapidly catabolize after absorption to avoid causing hepatotoxicity due to hepatic MTP inhibition. In previous reports, we have demonstrated that JTT-130 suppresses dietary lipid absorption in the small intestine without inducing hepatic steatosis. Thus, in this report, JTT-130 was administered to hyperlipidemic animals fed a Western diet to investigate the effect of intestinal MTP inhibition on lipid metabolism and progression of atherosclerosis.JTT-130 potently lowered plasma non-high density lipoprotein-cholesterol, and elevated plasma high density lipoprotein-cholesterol (HDL-C), indicating improvement in atherogenic index in hamsters. HDL fractions obtained after two weeks treatment with JTT-130 significantly increased the efflux of cholesterol from macrophages, as an index parameter of HDL function. Furthermore, long-term treatment with JTT-130 also improved the plasma lipid profile without inducing hepatic steatosis in rabbits, resulting in the suppression of atherosclerosis formation in aortas.From these results, JTT-130 ameliorates lipid metabolism accompanied with the enhancement of the anti-atherosclerotic function of HDL, and attenuates the progression of atherosclerosis in hyperlipidemic animals. These findings indicate that intestinal MTP inhibition may be atherogenic in vivo and that JTT-130 may be a useful compound for the treatment of dyslipidemia and a potential anti-atherogenic drug.

Identification and Treatment of Patients with Homozygous Familial Hypercholesterolaemia: Information and Recommendations from a Middle East Advisory Panel.

We present clinical practice guidelines for the diagnosis and treatment of homozygous familial hypercholesterolaemia (HoFH) in the Middle East region. While guidelines are broadly applicable in Europe, in the Middle East we experience a range of confounding factors that complicate disease management to a point whereby the European guidance cannot be applied without significant modification. Specifically, for disease prevalence, the Middle East region has an established epidemic of diabetes and metabolic syndrome that can complicate treatment and mask a clinical diagnosis of HoFH. We have also a high incidence of consanguineous marriages, which increase the risk of transmission of recessive and homozygous genetic disorders. This risk is further augmented in autosomal dominant disorders such as familial hypercholesterolaemia (FH), in which a range of defective genes can be transmitted, all of which contribute to the phenotypic expression of the disease. In terms of treatment, we do not have access to lipoprotein apheresis on the same scale as in Europe, and there remains a significant reliance on statins, ezetimibe and the older plasma exchange methods. Additionally, we do not have widespread access to anti-apolipoprotein B therapies and microsomal transfer protein inhibitors. In order to adapt existing global guidance documents on HoFH to the Middle East region, we convened a panel of experts from Oman, Saudi Arabia, UAE, Iran and Bahrain to draft a regional guidance document for HoFH. We also included selected experts from outside the region. This panel statement will form the foundation of a detailed appraisal of the current FH management in the Middle Eastern population and thereby provide a suitable set of guidelines tailored for the region.

Mipomersen and lomitapide: Two new drugs for the treatment of homozygous familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a disease associated with very high plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. It is difficult in these high risk patients, exposed lifelong to very high LDL-C, to reach target LDL-C concentrations, which require >50% LDL-C reduction, even when on maximally tolerated statin therapy and on apheresis if available. Therefore, there is an unmet need for new therapeutic options for these patients. In 2013 two new drugs were approved for the treatment of homozygous FH, namely the apolipoprotein B synthesis inhibitor mipomersen and the microsomal transfer protein inhibitor lomitapide. Objective of this narrative review is to discuss the available evidence on the safety and efficacy profile of these new drugs.