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Antisenses working overtime in lipids

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Antisense oligonucleotides have proven effective at preventing protein synthesis as a result of their on-target specificity. Recent data from several clinical trials including a phase I trial targeting Lp(a), published in The Lancet, highlight the therapeutic potential of antisense oligonucleotides in regulating plasma lipid levels.

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Figure 1: Targeted action of apo(a) ASO.

References

  1. Tsimikas, S. et al. Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study. Lancet http://dx.doi.org/10.1016/S0140-6736(15)61252-1.

  2. Gaudet, D. et al. Antisense inhibition of apolipoprotein C-III in patients with hypertriglyceridemia. N. Engl. J. Med. 373, 438–447 (2015).

    Article  CAS  Google Scholar 

  3. Sabatine, M. S. et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372, 1500–1509 (2015).

    Article  CAS  Google Scholar 

  4. Robinson, J. G. et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372, 1489–1499 (2015).

    Article  CAS  Google Scholar 

  5. Koschinsky, M. L. & Boffa, M. B. Lipoprotein(a): an important cardiovascular risk factor and a clinical conundrum. Endocrinol. Metab. Clin. North. Am. 43, 949–962 (2014).

    Article  Google Scholar 

  6. Clarke, R. et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N. Engl. J. Med. 361, 2518–2528 (2009).

    Article  CAS  Google Scholar 

  7. Kamstrup, P. R., Tybjaerg-Hansen, A. & Nordestgaard, B. G. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J. Am. Coll. Cardiol. 63, 470–477 (2014).

    Article  CAS  Google Scholar 

  8. Alonso, R. et al. Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation. J. Am. Coll. Cardiol. 63, 1982–1989 (2014).

    Article  CAS  Google Scholar 

  9. Thomas, G. S. et al. 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. 62, 2178–2184 (2013).

    Article  CAS  Google Scholar 

  10. Romagnuolo, R. et al. Lipoprotein(a) catabolism is regulated by proprotein convertase subtilisin/kexin type 9 through the low density lipoprotein receptor. J. Biol. Chem. 290, 11649–11662 (2015).

    Article  CAS  Google Scholar 

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Acknowledgements

R.A.H. is supported by grants from the Canadian Institutes of Health Research (Foundation Program), the Heart and Stroke Foundation (Project G-15-0009214), and Genome Canada (through Genome Quebec). S.M.K.F. is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Canada Graduate Scholarship.

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Authors and Affiliations

  1. Departments of Biochemistry and Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, Room 4288, 1151 Richmond Street North, London, N6A 5K8, ON, Canada

    Sali M. K. Farhan & Robert A. Hegele

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  1. Sali M. K. Farhan
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  2. Robert A. Hegele
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Correspondence to Robert A. Hegele.

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Competing interests

R.A.H. consults for Aegerion, Amgen, Boston Heart Diagnostics, ISIS, Lilly, Merck, Pfizer, Sanofi and Valeant Pharmaceuticals. S.M.K.F. declares no competing interests.

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Farhan, S., Hegele, R. Antisenses working overtime in lipids. Nat Rev Endocrinol 11, 574–576 (2015). https://doi.org/10.1038/nrendo.2015.146

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