Advanced search
Publication Cover
Expert Review of Cardiovascular Therapy Volume 10, 2012 - Issue 10
Submit an article Journal homepage
93
Views
3
CrossRef citations to date
0
Altmetric
Review

New treatments on the horizon for familial hypercholesterolemia

Marybeth U Allian-Sauer Division of Cardiology, University of Colorado Denver, 13199 E. Montview Boulevard, Suite 200, Aurora, CO 80045, USA. [email protected]; Division of Cardiology, University of Colorado Denver, 13199 E. Montview Boulevard, Suite 200, Aurora, CO 80045, USA. [email protected]
&
James M Falko Division of Endocrinology, University of Colorado Denver, Endocrinology Clinic, Mail Stop F732, Anschutz Outpatient Pavilion, 6th Floor West, Room 6600, 1635 Aurora Court, Aurora, CO 80045, USA; Division of Endocrinology, University of Colorado Denver, Endocrinology Clinic, Mail Stop F732, Anschutz Outpatient Pavilion, 6th Floor West, Room 6600, 1635 Aurora Court, Aurora, CO 80045, USA
Pages 1227-1237 | Published online: 10 Jan 2014

References

  • Marais AD, Raal FJ, Stein EA et al. A dose-titration and comparative study of rosuvastatin and atorvastatin in patients with homozygous familial hypercholesterolaemia. Atherosclerosis 197(1), 400–406 (2008).
  • Allian-Sauer MU, Falko JM. A review of the role of apheresis in the management of familial hypercholesterolemia and elevated lipoprotein (a) levels. Clin. Lipidol. 6, 523–538 (2011).
  • Merki E, Graham MJ, Mullick AE et al. Antisense oligonucleotide directed to human apolipoprotein B-100 reduces lipoprotein(a) levels and oxidized phospholipids on human apolipoprotein B-100 particles in lipoprotein(a) transgenic mice. Circulation 118(7), 743–753 (2008).
  • Steinberg D, Avigan J, Feigelson EB. Effects of triparanol (mer-29) on cholesterol biosynthesis and on blood sterol levels in man. J. Clin. Invest. 40(5), 884–893 (1961).
  • Gagné C, Gaudet D, Bruckert E; Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation 105(21), 2469–2475 (2002).
  • Stein E, Stender S, Mata P et al.; Ezetimibe Study Group. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am. Heart J. 148(3), 447–455 (2004).
  • Zema MJ. Colesevelam HCl and ezetimibe combination therapy provides effective lipid-lowering in difficult-to-treat patients with hypercholesterolemia. Am. J. Ther. 12(4), 306–310 (2005).
  • Pisciotta L, Fasano T, Bellocchio A et al. Effect of ezetimibe coadministered with statins in genotype-confirmed heterozygous FH patients. Atherosclerosis 194(2), e116–e122 (2007).
  • Pitsavos C, Skoumas I, Tousoulis D et al. The impact of ezetimibe and high-dose of statin treatment on LDL levels in patients with heterozygous familial hypercholesterolemia. Int. J. Cardiol. 134(2), 280–281 (2009).
  • Yeste D, Chacón P, Clemente M, Albisu MA, Gussinyé M, Carrascosa A. Ezetimibe as monotherapy in the treatment of hypercholesterolemia in children and adolescents. J. Pediatr. Endocrinol. Metab. 22(6), 487–492 (2009).
  • Li H, Dong B, Park SW, Lee HS, Chen W, Liu J. Hepatocyte nuclear factor 1 alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. J. Biol. Chem. 284(42), 28885–28895 (2009).
  • Abidi P, Zhou Y, Jiang JD, Liu J. Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine. Arterioscler. Thromb. Vasc. Biol. 25(10), 2170–2176 (2005).
  • Harris WS, Dujovne CA, von Bergmann K et al. Effects of the ACAT inhibitor CL 277,082 on cholesterol metabolism in humans. Clin. Pharmacol. Ther. 48(2), 189–194 (1990).
  • Hainer JW, Terry JG, Connell JM et al. Effect of the acyl-CoA:cholesterol acyltransferase inhibitor DuP 128 on cholesterol absorption and serum cholesterol in humans. Clin. Pharmacol. Ther. 56(1), 65–74 (1994).
  • Dominick MA, Bobrowski WA, MacDonald JR, Gough AW. Morphogenesis of a zone-specific adrenocortical cytotoxicity in guinea pigs administered PD 132301-2, an inhibitor of acyl-CoA:cholesterol acyltransferase. Toxicol. Pathol. 21(1), 54–62 (1993).
  • Dominick MA, McGuire EJ, Reindel JF, Bobrowski WF, Bocan TM, Gough AW. Subacute toxicity of a novel inhibitor of acyl-CoA: cholesterol acyltransferase in beagle dogs. Fundam. Appl. Toxicol. 20(2), 217–224 (1993).
  • Willner EL, Tow B, Buhman KK et al. Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Proc. Natl Acad. Sci. U.S.A. 100(3), 1262–1267 (2003).
  • Lee RG, Kelley KL, Sawyer JK, Farese RV Jr, Parks JS, Rudel LL. Plasma cholesteryl esters provided by lecithin:cholesterol acyltransferase and acyl-coenzyme a:cholesterol acyltransferase 2 have opposite atherosclerotic potential. Circ. Res. 95(10), 998–1004 (2004).
  • Tardif JC, Grégoire J, L’Allier PL et al.; Avasimibe and Progression of Lesions on UltraSound (A-PLUS) Investigators. Effects of the acyl coenzyme A:cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions. Circulation 110(21), 3372–3377 (2004).
  • Nissen SE, Tuzcu EM, Brewer HB et al.; ACAT Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE) Investigators. Effect of ACAT inhibition on the progression of coronary atherosclerosis. N. Engl. J. Med. 354(12), 1253–1263 (2006).
  • Meuwese MC, de Groot E, Duivenvoorden R et al.; CAPTIVATE Investigators. ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial. JAMA 301(11), 1131–1139 (2009).
  • Brousseau ME, Schaefer EJ, Wolfe ML et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N. Engl. J. Med. 350(15), 1505–1515 (2004).
  • Dansky HM, Bloomfield D, Gibbons P et al. Efficacy and safety after cessation of treatment with the cholesteryl ester transfer protein inhibitor anacetrapib (MK-0859) in patients with primary hypercholesterolemia or mixed hyperlipidemia. Am. Heart J. 162(4), 708–716 (2011).
  • Nicholls SJ, Brewer HB, Kastelein JJ et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA 306(19), 2099–2109 (2011).
  • Ellis CJ, Scott R. Statins and coenzyme Q10. Lancet 361(9363), 1134–1135 (2003).
  • Nishimoto T, Amano Y, Tozawa R et al. Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro. Br. J. Pharmacol. 139(5), 911–918 (2003).
  • Amano Y, Nishimoto T, Tozawa R, Ishikawa E, Imura Y, Sugiyama Y. Lipid-lowering effects of TAK-475, a squalene synthase inhibitor, in animal models of familial hypercholesterolemia. Eur. J. Pharmacol. 466(1–2), 155–161 (2003).
  • Nishimoto T, Ishikawa E, Anayama H et al. Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs. Toxicol. Appl. Pharmacol. 223(1), 39–45 (2007).
  • Piper E, Graham P, Chen Y. TAK-475, a squalene synthase inhibitor, improves lipid profile in hyperlipidemic subjects. Circulation 114 (Suppl.), 288 (2006).
  • Perez KA, Chen Y. Addition of TAK-475 to atorvastatin provides incremental lipid benefits. Circulation 114(18 Suppl.), 113–114 (2006).
  • Bays HE, Weiss RJ, James RM et al. Lapaqistat acetate monotherapy: effects of a novel squalene synthase inhibitor on LDL-C levels and other lipid parameters in patients with primary hypercholesterolemia. Circulation 116(Suppl.), 116 (2007).
  • Davidson MH, Maki KC, Zavoral JH et al. Lapaquistat acetate, a novel squalene synthase inhibitor, co-administered with atorvastatin reduces plasma lipids and C-reactive protein levels in subjects with primary hypercholesterolemia [abstract 193]. Circulation 116(Suppl. 17), 193 (2007).
  • Powell LM, Wallis SC, Pease RJ, Edwards YH, Knott TJ, Scott J. A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell 50(6), 831–840 (1987).
  • Fattal E, Bochot A. State of the art and perspectives for the delivery of antisense oligonucleotides and siRNA by polymeric nanocarriers. Int. J. Pharm. 364(2), 237–248 (2008).
  • Yu RZ, Kim TW, Hong A, Watanabe TA, Gaus HJ, Geary RS. Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100. Drug Metab. Dispos. 35(3), 460–468 (2007).
  • Yu RZ, Geary RS, Flaim JD et al. Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2’-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe. Clin. Pharmacokinet. 48(1), 39–50 (2009).
  • Khoo B, Roca X, Chew SL, Krainer AR. Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB. BMC Mol. Biol. 8, 3 (2007).
  • Soutschek J, Akinc A, Bramlage B et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432(7014), 173–178 (2004).
  • Nishina K, Unno T, Uno Y et al. Efficient in vivo delivery of siRNA to the liver by conjugation of alpha-tocopherol. Mol. Ther. 16(4), 734–740 (2008).
  • Zimmermann TS, Lee AC, Akinc A et al. RNAi-mediated gene silencing in non-human primates. Nature 441(7089), 111–114 (2006).
  • Crooke RM, Graham MJ, Lemonidis KM, Whipple CP, Koo S, Perera RJ. An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis. J. Lipid Res. 46(5), 872–884 (2005).
  • 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 114(16), 1729–1735 (2006).
  • 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. 33(9), 1142–1149 (2012).
  • 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. 105(10), 1413–1419 (2010).
  • 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. 55(15), 1611–1618 (2010).
  • Visser ME, Akdim F, Tribble DL et al. Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia. J. Lipid Res. 51(5), 1057–1062 (2010).
  • Heiss G, Tamir I, Davis CE et al. Lipoprotein-cholesterol distributions in selected North American populations: the lipid research clinics program prevalence study. Circulation 61(2), 302–315 (1980).
  • Contois JH, McNamara JR, Lammi-Keefe CJ, Wilson PW, Massov T, Schaefer EJ. Reference intervals for plasma apolipoprotein B determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study. Clin. Chem. 42(4), 515–523 (1996).
  • Schonfeld G, Yue P, Lin X, Chen Z. Fatty liver and insulin resistance: not always linked. Trans. Am. Clin. Climatol. Assoc. 119, 217–223; discussion 223 (2008).
  • Amaro A, Fabbrini E, Kars M et al. Dissociation between intrahepatic triglyceride content and insulin resistance in familial hypobetalipoproteinemia. Gastroenterology 139(1), 149–153 (2010).
  • 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 375(9719), 998–1006 (2010).
  • Farese RV Jr. The nine lives of ACAT inhibitors. Arterioscler. Thromb. Vasc. Biol. 26(8), 1684–1686 (2006).
  • Leiper JM, Bayliss JD, Pease RJ, Brett DJ, Scott J, Shoulders CC. Microsomal triglyceride transfer protein, the abetalipoproteinemia gene product, mediates the secretion of apolipoprotein B-containing lipoproteins from heterologous cells. J. Biol. Chem. 269(35), 21951–21954 (1994).
  • Patel SB, Grundy SM. Interactions between microsomal triglyceride transfer protein and apolipoprotein B within the endoplasmic reticulum in a heterologous expression system. J. Biol. Chem. 271(31), 18686–18694 (1996).
  • Wetterau JR, Aggerbeck LP, Bouma ME et al. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science 258(5084), 999–1001 (1992).
  • Chandler CE, Wilder DE, Pettini JL et al. CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans. J. Lipid Res. 44(10), 1887–1901 (2003).
  • Wetterau JR, Gregg RE, Harrity TW et al. An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits. Science 282(5389), 751–754 (1998).
  • Farnier M, Stein E, Megnien S et al. Efficacy and safety of implitapide, a microsomal triglyceride transport protein inhibitor in patients with primary hypercholesterolemia. Abstract Book of the X!V International Symposium on Drugs Affecting Lipid Metabolism, New York, September 9–12, 2001.
  • Cuchel M, Bloedon LT, Szapary PO et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N. Engl. J. Med. 356(2), 148–156 (2007).
  • Samaha FF, McKenney J, Bloedon LT, Sasiela WJ, Rader DJ. Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia. Nat. Clin. Pract. Cardiovasc. Med. 5(8), 497–505 (2008).
  • Billheimer J, Cromley D, Sasiela W, Rader DJ. Menhaden oil ameliorates the steatosis caused by inhibition of microsomal triglyceride transfer protein. In: American Diabetes Association’s 69th Scientific Sessions. Boston, MA, USA (2009).
  • Grover GJ, Mellström K, Ye L et al. Selective thyroid hormone receptor-beta activation: a strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability. Proc. Natl Acad. Sci. USA 100(17), 10067–10072 (2003).
  • Grover GJ, Egan DM, Sleph PG et al. Effects of the thyroid hormone receptor agonist GC-1 on metabolic rate and cholesterol in rats and primates: selective actions relative to 3,5,3´-triiodo-l-thyronine. Endocrinology 145(4), 1656–1661 (2004).
  • Ness GC, Lopez D, Chambers CM et al. Effects of l-triiodothyronine and the thyromimetic L-94901 on serum lipoprotein levels and hepatic low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and apo A-I gene expression. Biochem. Pharmacol. 56(1), 121–129 (1998).
  • Shin DJ, Osborne TF. Thyroid hormone regulation and cholesterol metabolism are connected through Sterol Regulatory Element-Binding Protein-2 (SREBP-2). J. Biol. Chem. 278(36), 34114–34118 (2003).
  • Bennet A, Di Angelantonio E, Erqou S et al. Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data. Arch. Intern. Med. 168(6), 598–608 (2008).
  • Berkenstam A, Kristensen J, Mellström K et al. The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans. Proc. Natl Acad. Sci. USA 105(2), 663–667 (2008).
  • Ladenson PW, Kristensen JD, Ridgway EC et al. Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia. N. Engl. J. Med. 362(10), 906–916 (2010).
  • Konrad RJ, Troutt JS, Cao G. Effects of currently prescribed LDL-C-lowering drugs on PCSK9 and implications for the next generation of LDL-C-lowering agents. Lipids Health Dis. 10, 38 (2011).
  • Chan JC, Piper DE, Cao Q et al. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc. Natl Acad. Sci. USA 106(24), 9820–9825 (2009).
  • Frank-Kamenetsky M, Grefhorst A, Anderson NN et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc. Natl Acad. Sci. USA 105(33), 11915–11920 (2008).
  • Di Bartolo BA, Nicholls SJ, Bao S et al. The apolipoprotein A-I mimetic peptide ETC-642 exhibits anti-inflammatory properties that are comparable to high density lipoproteins. Atherosclerosis 217(2), 395–400 (2011).
  • Van Lenten BJ, Wagner AC, Jung CL et al. Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I. J. Lipid Res. 49(11), 2302–2311 (2008).

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.