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

  • Lipid and Metabolic Effects of Gastrointestinal Surgery (R. Cohen, Section Editor)
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Abstract

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.

Summary

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.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223(2):262–8.

    CAS  PubMed  Google Scholar 

  2. • Sjouke B, Kusters DM, Kindt I, et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype-phenotype relationship, and clinical outcome. Eur Heart J. 2015;36(9):560–5 The first publication that demonstrated the large phenotypic variability of patients with a genetic diagnosis of homozygous familial hypercholesterolaemia.

    PubMed  Google Scholar 

  3. Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Marais AD. Familial hypercholesterolaemia. Clin Biochem Rev. 2004;25(1):49–68.

    PubMed  PubMed Central  Google Scholar 

  5. Gaffney D, Forster L, Caslake MJ, et al. Comparison of apolipoprotein B metabolism in familial defective apolipoprotein B and heterogeneous familial hypercholesterolemia. Atherosclerosis. 2002;162(1):33–43.

    CAS  PubMed  Google Scholar 

  6. Abifadel M, Varret M, Rabes JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154–6.

    CAS  PubMed  Google Scholar 

  7. Garcia CK, Wilund K, Arca M, et al. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science. 2001;292(5520):1394–8.

    CAS  PubMed  Google Scholar 

  8. Wilund KR, Yi M, Campagna F, et al. Molecular mechanisms of autosomal recessive hypercholesterolemia. Hum Mol Genet. 2002;11(24):3019–30.

    CAS  PubMed  Google Scholar 

  9. Raal FJ, Sjouke B, Hovingh GK, Isaac BF. Phenotype diversity among patients with homozygous familial hypercholesterolemia: a cohort study. Atherosclerosis. 2016;248:238–44.

    CAS  PubMed  Google Scholar 

  10. Santos RD. Expression of LDLRs (Low-Density Lipoprotein Receptors), Dyslipidemia severity, and response to PCSK9 (proprotein convertase subtilisin kexin type 9) inhibition in momozygous familial hypercholesterolemia: connecting the dots. Arterioscler Thromb Vasc Biol. 2018;38(3):481–3.

    CAS  PubMed  Google Scholar 

  11. Marais AD, Blom DJ, Firth JC. Statins in homozygous familial hypercholesterolemia. Curr Atheroscler Rep. 2002;4(1):19–25.

    CAS  PubMed  Google Scholar 

  12. Marais AD, Firth JC, Blom DJ. Homozygous familial hypercholesterolemia and its management. Semin Vasc Med. 2004;4(1):43–50.

    PubMed  Google Scholar 

  13. Gagne C, Gaudet D, Bruckert E, Ezetimibe Study G. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation. 2002;105(21):2469–75.

    CAS  PubMed  Google Scholar 

  14. Feher MD, Webb JC, Patel DD, et al. Cholesterol-lowering drug therapy in a patient with receptor-negative homozygous familial hypercholesterolaemia. Atherosclerosis. 1993;103(2):171–80.

    CAS  PubMed  Google Scholar 

  15. Malloy MJ, Kane JP, Kunitake ST, Tun P. Complementarity of colestipol, niacin, and lovastatin in treatment of severe familial hypercholesterolemia. Ann Intern Med. 1987;107(5):616–23.

    CAS  PubMed  Google Scholar 

  16. Raal FJ, Pilcher GJ, Panz VR, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation. 2011;124(20):2202–7.

    CAS  PubMed  Google Scholar 

  17. Moorjani S, Roy M, Gagne C, et al. Homozygous familial hypercholesterolemia among French Canadians in Quebec Province. Arteriosclerosis. 1989;9(2):211–6.

    CAS  PubMed  Google Scholar 

  18. Kolansky DM, Cuchel M, Clark BJ, et al. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am J Cardiol. 2008;102(11):1438–43.

    PubMed  Google Scholar 

  19. Sanna C, Stephenne X, Revencu N, et al. Homozygous familial hypercholesterolemia in childhood: genotype-phenotype description, established therapies and perspectives. Atherosclerosis. 2016;247:97–104.

    CAS  PubMed  Google Scholar 

  20. Stein EA, Honarpour N, Wasserman SM, Xu F, Scott R, Raal FJ. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013;128(19):2113–20.

    CAS  PubMed  Google Scholar 

  21. • Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385(9965):341–50 This trial demonstrates the utility of PCSK9 inhibition with evolocumab in patients with homozygous familial hypercholesterolaemia.

    CAS  PubMed  Google Scholar 

  22. Raal FJ, Hovingh GK, Blom D, et al. Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diabetes Endocrinol. 2017;5(4):280–290.

    CAS  Google Scholar 

  23. Forman MB, Baker SG, Mieny CJ, et al. Treatment of homozygous familial hypercholesterolaemia with portacaval shunt. Atherosclerosis. 1982;41(2-3):349–61.

    CAS  PubMed  Google Scholar 

  24. McNamara DJ, Ahrens EH Jr, Kolb R, et al. Treatment of familial hypercholesterolemia by portacaval anastomosis: effect on cholesterol metabolism and pool sizes. Proc Natl Acad Sci U S A. 1983;80(2):564–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Starzl TE, Chase HP, Ahrens EH Jr, et al. Portacaval shunt in patients with familial hypercholesterolemia. Ann Surg. 1983;198(3):273–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Dupont J, Lumb WV, Nelson AW, Seegmiller JP, Hotchkiss D, Chase HP. Portacaval shunt as treatment for hypercholesterolemia. Metabolic and morphological effects in a swine model. Atherosclerosis. 1985;58(1-3):205–22.

    CAS  PubMed  Google Scholar 

  27. Hoeg JM, Demosky SJ Jr, Schaefer EJ, Starzl TE, Porter KA, Brewer HB Jr. The effect of portacaval shunt on hepatic lipoprotein metabolism in familial hypercholesterolemia. J Surg Res. 1985;39(5):369–77.

    CAS  PubMed  Google Scholar 

  28. Bilheimer DW. Portacaval shunt surgery and liver transplantation in the treatment of homozygous familial hypercholesterolemia. Prog Clin Biol Res. 1988;255:295–304.

    CAS  PubMed  Google Scholar 

  29. Revell SP, Noble-Jamieson G, Johnston P, Rasmussen A, Jamieson N, Barnes ND. Liver transplantation for homozygous familial hypercholesterolaemia. Arch Dis Child. 1995;73(5):456–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Castilla Cabezas JA, Lopez-Cillero P, Jimenez J, et al. Role of orthotopic liver transplant in the treatment of homozygous familial hypercholesterolemia. Rev Esp Enferm Dig. 2000;92(9):601–8.

    CAS  PubMed  Google Scholar 

  31. Page MM, Ekinci EI, Jones RM, Angus PW, Gow PJ, O'Brien RC. Liver transplantation for the treatment of homozygous familial hypercholesterolaemia in an era of emerging lipid-lowering therapies. Intern Med J. 2014;44(6):601–4.

    CAS  PubMed  Google Scholar 

  32. Julius U. History of lipidology and lipoprotein apheresis. Atheroscler Suppl. 2017;30:1–8.

    PubMed  Google Scholar 

  33. Stefanutti C, Thompson GR. Lipoprotein apheresis in the management of familial hypercholesterolaemia: historical perspective and recent advances. Curr Atheroscler Rep. 2015;17(1):465.

    PubMed  Google Scholar 

  34. Grutzmacher P, Kleinert C, Dorbath C, Ohm B. Indications for apheresis as an ultima ratio treatment of refractory hyperlipidemias. Clin Res Cardiol Suppl. 2015;10:2–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Wetterau JR, Aggerbeck LP, Laplaud PM, McLean LR. Structural properties of the microsomal triglyceride-transfer protein complex. Biochemistry. 1991;30(18):4406–12.

    CAS  PubMed  Google Scholar 

  36. Wetterau JR, Aggerbeck LP, Bouma ME, et al. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science. 1992;258(5084):999–1001.

    CAS  PubMed  Google Scholar 

  37. Gregg RE, Wetterau JR. The molecular basis of abetalipoproteinemia. Curr Opin Lipidol. 1994;5(2):81–6.

    CAS  PubMed  Google Scholar 

  38. Welty FK. Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol. 2014;25(3):161–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Hooper AJ, Burnett JR, Watts GF. Contemporary aspects of the biology and therapeutic regulation of the microsomal triglyceride transfer protein. Circ Res. 2015;116(1):193–205.

    CAS  PubMed  Google Scholar 

  40. Wetterau JR, Gregg RE, Harrity TW, et al. An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits. Science. 1998;282(5389):751–4.

    CAS  PubMed  Google Scholar 

  41. Cuchel M, Bloedon LT, Szapary PO, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007;356(2):148–56.

    CAS  PubMed  Google Scholar 

  42. Cuchel M, Meagher EA, du Toit TH, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013;381(9860):40–6.

    CAS  PubMed  Google Scholar 

  43. Stefanutti C, Blom DJ, Averna MR, et al. The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia-a post-hoc analysis of a Phase 3, single-arm, open-label trial. Atherosclerosis. 2015;240(2):408–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. •• Blom DJ, Averna MR, Meagher EA, et al. Long-term efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in patients with homozygous familial hypercholesterolemia. Circulation. 2017;136(3):332–5 This publication provides long-term data on the safety and efficacy of lomitapide in patients who participated in the extension study.

    CAS  PubMed  Google Scholar 

  45. Harada-Shiba M, Ikewaki K, Nohara A, et al. Efficacy and safety of lomitapide in Japanese patients with homozygous familial hypercholesterolemia. J Atheroscler Thromb. 2017;24(4):402–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Nohara A, Otsubo Y, Yanagi K, et al. Safety and efficacy of lomitapide in Japanese patients with homozygous familial hypercholesterolemia (HoFH): results from the AEGR-733-301 long-term extension study. J Atheroscler Thromb. 2019;26(4):368–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Kolovou GD, Kolovou V, Papadopoulou A, Watts GF. MTP gene variants and response to lomitapide in patients with homozygous familial hypercholesterolemia. J Atheroscler Thromb. 2016;23(7):878–83.

    CAS  PubMed  Google Scholar 

  48. Blom DJ, Cuchel M, Ager M, Phillips H. Target achievement and cardiovascular event rates with lomitapide in homozygous familial hypercholesterolaemia. Orphanet J Rare Dis. 2018;13(1):96.

    PubMed  PubMed Central  Google Scholar 

  49. • Thompson GR, Blom DJ, Marais AD, Seed M, Pilcher GJ, Raal FJ. Survival in homozygous familial hypercholesterolaemia is determined by the on-treatment level of serum cholesterol. Eur Heart J. 2018;39(14):1162–1168.This publication demonstrates that outcome in patients with hoFH is determined by their response to treatment and the on-treatment cholesterol.

    Google Scholar 

  50. Leipold R, Raal F, Ishak J, Hovingh K, Phillips H. The effect of lomitapide on cardiovascular outcome measures in homozygous familial hypercholesterolemia: a modelling analysis. Eur J Prev Cardiol. 2017;24(17):1843–50.

    PubMed  Google Scholar 

  51. D'Erasmo L, Cefalu AB, Noto D, et al. Efficacy of lomitapide in the treatment of familial homozygous hypercholesterolemia: results of a real-world clinical Experience in Italy. Adv Ther. 2017;34(5):1200–10.

    CAS  PubMed  Google Scholar 

  52. Sperlongano S, Gragnano F, Natale F, et al. Lomitapide in homozygous familial hypercholesterolemia: cardiology perspective from a single-center experience. J Cardiovasc Med (Hagerstown). 2018;19(3):83–90.

    CAS  Google Scholar 

  53. Chacra APM, Ferrari MC, Rocha VZ, Santos RD. Case report: the efficiency and safety of lomitapide in a homozygous familial hypercholesterolemic child. J Clin Lipidol. 2019.

  54. Ben-Omran T, Masana L, Kolovou G, et al. Real-world outcomes with lomitapide use in paediatric patients with homozygous familial hypercholesterolaemia. Adv Ther. 2019;36(7):1786–1811.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Blom DJ, Fayad ZA, Kastelein JJ, et al. LOWER, a registry of lomitapide-treated patients with homozygous familial hypercholesterolemia: Rationale and design. J Clin Lipidol. 2016;10(2):273–82.

    PubMed  Google Scholar 

  56. Blom DJ, Fayad ZA, Kastelein JJ, et al. Long-term safety and efficacy of lomitapide in patients with homozygous familial hypercholesterolaemia: three-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER). JACC. 2018;71;(11). https://doi.org/10.1016/S0735-1097(18)30709-5.

    Google Scholar 

  57. Visser ME, Lammers NM, Nederveen AJ, et al. Hepatic steatosis does not cause insulin resistance in people with familial hypobetalipoproteinaemia. Diabetologia. 2011;54(8):2113–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Sacks FM, Stanesa M, Hegele RA. Progression to hepatitis and fibrosis secondary to lomitapide use--reply. JAMA Intern Med. 2014;174(9):1522–3.

    PubMed  Google Scholar 

  59. Kastelein JJ, Wedel MK, Baker BF, et al. Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation. 2006;114(16):1729–35.

    CAS  PubMed  Google Scholar 

  60. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375(9719):998–1006.

    CAS  PubMed  Google Scholar 

  61. Akdim F, Stroes ES, Sijbrands EJ, et al. Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J Am Coll Cardiol. 2010;55(15):1611–8.

    CAS  PubMed  Google Scholar 

  62. Akdim F, Tribble DL, Flaim JD, et al. Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia. Eur Heart J. 2011;32(21):2650–9.

    CAS  PubMed  Google Scholar 

  63. Akdim F, Visser ME, Tribble DL, et al. Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia. Am J Cardiol. 2010;105(10):1413–9.

    CAS  PubMed  Google Scholar 

  64. Flaim JD, Grundy JS, Baker BF, McGowan MP, Kastelein JJ. Changes in mipomersen dosing regimen provide similar exposure with improved tolerability in randomized placebo-controlled study of healthy volunteers. J Am Heart Assoc. 2014;3(2):e000560.

    PubMed  PubMed Central  Google Scholar 

  65. McGowan MP, Tardif JC, Ceska R, et al. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PloS one. 2012;7(11):e49006.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Reeskamp LF, Kastelein JJP, Moriarty PM, et al. Safety and efficacy of mipomersen in patients with heterozygous familial hypercholesterolemia. Atherosclerosis. 2019;280:109–17.

    CAS  PubMed  Google Scholar 

  67. Stein EA, Dufour R, Gagne C, et al. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation. 2012;126(19):2283–92.

    CAS  PubMed  Google Scholar 

  68. Thomas GS, Cromwell WC, Ali S, Chin W, Flaim JD, Davidson M. Mipomersen, an apolipoprotein B synthesis inhibitor, reduces atherogenic lipoproteins in patients with severe hypercholesterolemia at high cardiovascular risk: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2013;62(23):2178–84.

    CAS  PubMed  Google Scholar 

  69. Visser ME, Kastelein JJ, Stroes ES. Apolipoprotein B synthesis inhibition: results from clinical trials. Curr Opin Lipidol. 2010;21(4):319–23.

    CAS  PubMed  Google Scholar 

  70. Visser ME, Wagener G, Baker BF, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial. Eur Heart J. 2012;33(9):1142–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Waldmann E, Vogt A, Crispin A, Altenhofer J, Riks I, Parhofer KG. Effect of mipomersen on LDL cholesterolholesterol in patients with severe LDL-hypercholesterolaemia and atherosclerosis treated by lipoprotein apheresis (The MICA-Study). Atherosclerosis. 2017;259:20–5.

    CAS  PubMed  Google Scholar 

  72. •• Fogacci F, Ferri N, Toth PP, Ruscica M, Corsini A, AFG C. Efficacy and safety of mipomersen: a systematic review and meta-analysis of randomized clinical trials. Drugs. 2019;79(7):751–766.This meta-analysis summarises and analyses the current clinical trial data for mipomersen.

    CAS  PubMed  Google Scholar 

  73. Santos RD, Duell PB, East C, et al. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension. Eur Heart J. 2013;36(9):566–75.

    PubMed  PubMed Central  Google Scholar 

  74. Duell PB, Santos RD, Kirwan BA, Witztum JL, Tsimikas S, Kastelein JJP. Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia. J Clin Lipidol. 2016;10(4):1011–21.

    PubMed  Google Scholar 

  75. Hashemi N, Odze RD, McGowan MP, Santos RD, Stroes ES, Cohen DE. Liver histology during mipomersen therapy for severe hypercholesterolemia. J Clin Lipidol. 2014;8(6):606–11.

    PubMed  PubMed Central  Google Scholar 

  76. Nielsen LB. Lipoprotein production by the heart: a novel pathway of triglyceride export from cardiomyocytes. Scand J Clin Lab Invest Suppl. 2002;237:35–40.

    CAS  PubMed  Google Scholar 

  77. Nielsen LB, Bartels ED, Bollano E. Overexpression of apolipoprotein B in the heart impedes cardiac triglyceride accumulation and development of cardiac dysfunction in diabetic mice. J Biol Chem. 2002;277(30):27014–20.

    CAS  PubMed  Google Scholar 

  78. Nielsen LB, Perko M, Arendrup H, Andersen CB. Microsomal triglyceride transfer protein gene expression and triglyceride accumulation in hypoxic human hearts. Arterioscler Thromb Vasc Biol. 2002;22(9):1489–94.

    CAS  PubMed  Google Scholar 

  79. Yokoyama M, Yagyu H, Hu Y, et al. Apolipoprotein B production reduces lipotoxic cardiomyopathy: studies in heart-specific lipoprotein lipase transgenic mouse. J Biol Chem. 2004;279(6):4204–11.

    CAS  PubMed  Google Scholar 

  80. Ramunddal T, Lindbom M, Scharin-Tang M, Stillemark-Billton P, Boren J, Omerovic E. Overexpression of apolipoprotein-B improves cardiac function and increases survival in mice with myocardial infarction. Biochem Biophys Res Commun. 2009;385(3):336–40.

    CAS  PubMed  Google Scholar 

  81. Zamel R, Khan R, Pollex RL, Hegele RA. Abetalipoproteinemia: two case reports and literature review. Orphanet J Rare Dis. 2008;3:19.

    PubMed  PubMed Central  Google Scholar 

  82. Liu Y, Conlon DM, Bi X, et al. Lack of MTTP Activity in pluripotent stem cell-derived hepatocytes and cardiomyocytes abolishes apoB secretion and increases cell stress. Cell Rep. 2017;19(7):1456–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Blom DJ, Marais AD. Evolocumab for the treatment of homozygous familial hypercholesterolaemia. Expert Opin Orphan D. 2016.

  84. Gaudet D, Gipe DA, Pordy R, et al. ANGPTL3 inhibition in homozygous familial hypercholesterolemia. New Engl J Med. 2017;377(3):296–7.

    PubMed  Google Scholar 

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Funding

RDS is a recipient of a scholarship from the Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq) process no. 303734/2018-3.

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Authors and Affiliations

  1. Department of Medicine, Division of Lipidology and Hatter Institute for Cardiovascular Research in Africa, University of Cape Town, 4th Floor Chris Barnard Building, Anzio Road, 7925 Observatory, Cape Town, South Africa

    Dirk J. Blom

  2. Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa

    Frederick J. Raal

  3. Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil

    Raul D. Santos

  4. Hospital Israelita Albert Einstein, Sao Paulo, Brazil

    Raul D. Santos

  5. Division of Chemical Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa

    A. David Marais

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  1. Dirk J. Blom
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Correspondence to Dirk J. Blom.

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Conflict of Interest

Dirk J. Blom has received honoraria related to consulting, research and or speaker activities from: Aegerion, Akcea, Amgen, AstraZeneca, MSD, Novo-Nordisk, Sanofi, Regeneron. DJB chairs the LOWER registry steering committee. Frederick J. Raal has received research grants, honoraria or consulting fees for professional input and/or delivered lectures from Sanofi, Regeneron, Amgen and The Medicines Company. Raul D. Santos has received honoraria related to consulting, research and/or speaker activities from: Akcea, Amgen, AstraZeneca, Biolab, Esperion, Kowa, Merck, MSD, Novo-Nordisk, Sanofi, and Regeneron. A. David Marais has received a grant for studies from Sanofi and Aegerion.

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Blom, D.J., Raal, F.J., Santos, R.D. et al. Lomitapide and Mipomersen—Inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 Synthesis. Curr Atheroscler Rep 21, 48 (2019). https://doi.org/10.1007/s11883-019-0809-3

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