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Biologic therapies for dyslipidemia

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Abstract

Biologic therapies involve the utilization of proteins, DNA, antibodies, or other substances derived or synthesized from living tissue for therapeutic effects. There are several biologic therapies in clinical development for the prevention and treatment of atherosclerosis. The most advanced in human trials are apolipoprotein mimetics, which include apolipoprotein A-1 Milano and phospholipid complexes. Infusions of these apolipoprotein mimetics have been demonstrated to reduce atherosclerotic development in both animal models and humans. Autoimmunization to create neutralizing antibodies to cholesteryl ester transfer protein is also in human trials. Gene therapies to reduce low-density lipoproteins and increase high-density lipoproteins are on the horizon, but the ability to safely prolong gene expression in humans will require the development of novel vectors.

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References and Recommended Reading

  1. Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, et al.: Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000, 288:669–672.

    Article  PubMed  CAS  Google Scholar 

  2. Lehrman S: Virus treatment questioned after gene therapy death. Nature 1999, 401:517–518.

    Article  PubMed  CAS  Google Scholar 

  3. Ferber D: Gene therapy. Safer and virus-free? Science 2001, 294:1638–1642.

    Article  PubMed  CAS  Google Scholar 

  4. Freedman SB: Clinical trials of gene therapy for atherosclerotic cardiovascular disease. Curr Opin Lipidol 2002, 13:653–661.

    Article  PubMed  CAS  Google Scholar 

  5. Bekeredjian R, Chen S, Frenkel PA, et al.: Ultrasound-targeted microbubble destruction can repeatedly direct highly specific plasmid expression to the heart. Circulation 2003, 108:1022–1026.

    Article  PubMed  Google Scholar 

  6. Raper SE, Grossman M, Rader DJ, et al.: Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia. Ann Surg 1996, 223:116–126.

    Article  PubMed  CAS  Google Scholar 

  7. Grossman M, Rader DJ, Muller DW, et al.: A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia. Nat Med 1995, 1:1148–1154.

    Article  PubMed  CAS  Google Scholar 

  8. Grossman M, Raper SE, Kozarsky K, et al.: Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nat Genet 1994, 6:335–341.

    Article  PubMed  CAS  Google Scholar 

  9. Plump AS, Scott CJ, Breslow JL: Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci USA 1994, 91:9607–9611.

    Article  PubMed  CAS  Google Scholar 

  10. Navab M, Anantharamaiah GM, Hama S, et al.: Oral administration of an apo A-I mimetic peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol. Circulation 2002, 105:290–292.

    Article  PubMed  CAS  Google Scholar 

  11. Shah PK, Yano J, Reyes O, et al.: High-dose recombinant apolipoprotein A-Imilano mobilizes tissue cholesterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein E-deficient mice: potential implications for acute plaque stabilization. Circulation 2001, 103:3047–3050.

    PubMed  CAS  Google Scholar 

  12. Chiesa G, Sirtori CR: Apolipoprotein A-IMilano: current perspectives. Curr Opin Lipidol 2003, 14:159–163.

    Article  PubMed  CAS  Google Scholar 

  13. Chiesa G, Sirtori CR: Recombinant apolipoprotein A-I(Milano): a novel agent for the induction of regression of atherosclerotic plaques. Ann Med 2003, 35:267–273.

    Article  PubMed  Google Scholar 

  14. Chiesa G, Monteggia E, Marchesi M, et al.: Recombinant apolipoprotein A-I(Milano) infusion into rabbit carotid artery rapidly removes lipid from fatty streaks. Circ Res 2002, 90:974–980.

    Article  PubMed  CAS  Google Scholar 

  15. Eriksson M, Carlson LA, Miettinen TA, Angelin B: Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans. Circulation 1999, 100:594–598.

    PubMed  CAS  Google Scholar 

  16. Angelin B, Parini P, Eriksson M: Reverse cholesterol transport in man: promotion of fecal steroid excretion by infusion of reconstituted HDL. Atheroscler Suppl 2002, 3:23–30.

    Article  PubMed  CAS  Google Scholar 

  17. Newton RS, Krause BR: HDL therapy for the acute treatment of atherosclerosis. Atheroscler Suppl 2002, 3:31–38.

    Article  PubMed  CAS  Google Scholar 

  18. Esperion Therapeutics, Inc.: Regression of atherosclerosis seen with ETC-216 (AIM). News release: June 26, 2003.

  19. Esperion Therapeutics: Internal data on file.

  20. Shimano H, Yamada N, Katsuki M, et al.: Plasma lipoprotein metabolism in transgenic mice overexpressing apolipoprotein E. Accelerated clearance of lipoproteins containing apolipoprotein B. J Clin Invest 1992, 90:2084–2091.

    PubMed  CAS  Google Scholar 

  21. Fan J, Ji ZS, Huang Y, et al.: Increased expression of apolipoprotein E in transgenic rabbits results in reduced levels of very low density lipoproteins and an accumulation of low density lipoproteins in plasma. J Clin Invest 1998, 101:2151–2164.

    PubMed  CAS  Google Scholar 

  22. Yamada N, Shimano H, Mokuno H, et al.: Increased clearance of plasma cholesterol after injection of apolipoprotein E into Watanabe heritable hyperlipidemic rabbits. Proc Natl Acad Sci U S A 1989, 86:665–669.

    Article  PubMed  CAS  Google Scholar 

  23. Datta G, Garber DW, Chung BH, et al.: Cationic domain 141-150 of apoE covalently linked to a class A amphipathic helix enhances atherogenic lipoprotein metabolism in vitro and in vivo. J Lipid Res 2001, 42:959–966.

    PubMed  CAS  Google Scholar 

  24. Tall AR: An overview of reverse cholesterol transport. Eur Heart J 1998, 19(suppl A):A31-A35.

    PubMed  CAS  Google Scholar 

  25. Whitlock ME, Swenson TL, Ramakrishman R, et al.: Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism. J Clin Invest 1989, 84:129–137.

    Article  PubMed  CAS  Google Scholar 

  26. Brown ML, Inazu A, Hesler CB, et al.: Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins. Nature 1989, 342:448–451.

    Article  PubMed  CAS  Google Scholar 

  27. Moriyama Y, Okamura T, Inazu A, et al.: A low prevalence of coronary heart disease among subjects with increased high density lipoprotein cholesterol levels, including those with plasma cholesteryl ester transfer protein deficiency. Prev Med 1998, 27:659–687.

    Article  PubMed  CAS  Google Scholar 

  28. Hirano K, Yamashita S, Nakajima N, et al.: Genetic cholesteryl ester transfer protein deficiency is extremely frequent in the Omagari area of Japan marked hyperalphalipoproteinemia caused by CETP gene mutation is not associated with longevity. Arterioscler Thromb Vasc Biol 1997, 17:1053–1059.

    PubMed  CAS  Google Scholar 

  29. Stein O, Stein Y: Atheroprotective mechanisms of HDL. Atherosclerosis 1999, 144:285–301.

    Article  PubMed  CAS  Google Scholar 

  30. Rittershaus CW, Miller DP, Thomas LJ, et al.: Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis. Arterioscler Thromb Vasc Biol 2000, 20:2106–2112.

    PubMed  CAS  Google Scholar 

  31. Davidson MH, Maki K, Umporowicz D, et al.: The safety and immunogenicity of a CETP vaccine in healthy adults. Atherosclerosis 2003, 169:113–120.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Preventive Cardiology, Rush University Medical Center, 1725 West Harrison Street, Suite 1159, 60612, Chicago, IL, USA

    Michael H. Davidson MD

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  1. Michael H. Davidson MD
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Davidson, M.H. Biologic therapies for dyslipidemia. Curr Atheroscler Rep 6, 69–72 (2004). https://doi.org/10.1007/s11883-004-0118-2

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  • DOI: https://doi.org/10.1007/s11883-004-0118-2

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