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Biased for benefit: Stimulating the world's most popular drug targets with more nuance

Nature Medicine volume 23, pages 649–651 (2017)Cite this article

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A Correction to this article was published on 01 July 2017

This article has been updated

Trevena was pinning its fortunes on a dramatic rewriting of cell-receptor theory that has taken place over the past three decades. Conventionally, drugs for many diseases have been designed to either shut a receptor down or cause it to become constantly active. But the new approach aims to tweak a receptor's outputs more subtly. The company hoped that such a nuance could be used to riff off heart medications used in chronic heart disease to design drugs for the more terrifying sudden onset of acute heart failure, which can rapidly cause death. In the old approach, drugs muted two key cell-receptor pathways, one of which helps to regulate blood pressure and fluid build-up, and the other of which affects how strongly the heart beats. A 'biased' drug would silence the first pathway to lower blood pressure, while activating the second pathway to strengthen the heartbeat.

Jonathan Violin, one of Trevena's scientific cofounders, was quietly confident that the team had found a winner. The 2012 trial results showed that dogs injected with TRV027 after induced heart failure fared better than dogs that did not receive the drug: their hearts were stronger and their kidneys functioned better1. Ideally, the drug could be administered to people who arrive at the hospital experiencing acute heart failure, and so help the nearly 1 million people in the US each year who experience this potentially fatal cardiac episode2. For some, acute heart failure presages a fatal heart attack; one in five die within a year. Despite the immense need, the arsenal of acute heart-failure treatments—diuretics to ease elevated blood pressure are the mainstay—has changed little since the 1970s3, and outcomes have remained stubbornly poor.

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Change history

  • 22 June 2017

    In the June 2017 issue, the story “Biased for benefit: Stimulating the world’s most popular drug targets with more nuance” (Nat. Med. 23, 649–651, 2017) misspelled the name of Laura Bohn’s postdoctoral advisor as Mark Caron. It should be spelled Marc Caron. The error has been corrected in the HTML and PDF versions of the article.

References

  1. Boerrigter, G. et al. Circ. Heart Fail. 5, 627–634 (2012).

    Article  CAS  Google Scholar 

  2. Benjamin, E.J. et al. Circ. 135, e146–e603 (2017).

    Article  Google Scholar 

  3. Collins, S. et al. J. Cardiol. Fail. 21, 27–43 (2015).

    Article  Google Scholar 

  4. Santos, R. et al. Nat. Rev. Drug Discov. 16, 19–34 (2017).

    Article  CAS  Google Scholar 

  5. Rajagopal, K. et al. Proc. Nat. Acad. Sci. USA 103, 16284–16289 (2006).

    Article  CAS  Google Scholar 

  6. Aplin, M. et al. Basic Clin. Pharmacol. Toxicol. 100, 289–295 (2007).

    Article  CAS  Google Scholar 

  7. Kim, K.S. et al. Am. J. Physiol. Heart. Circ. Physiol. 303, H1001–H1010 (2012).

    Article  CAS  Google Scholar 

  8. Luttrell, L.M. et al. Science 283, 655–661 (1999).

    Article  CAS  Google Scholar 

  9. Pang, P.S. et al. Eur. Heart J. 10.1093/eurheartj/ehx196 (2017).

  10. Pradhan, A.A. et al. Br. J. Pharmacol. 167, 960–969 (2012).

    Article  CAS  Google Scholar 

  11. Nozaki, C. et al. J. Pharmacol. Exp. Ther. 342, 799–807 (2012).

    Article  CAS  Google Scholar 

  12. Bohn, L.M. et al. Science 286, 2495–2498 (1999).

    Article  CAS  Google Scholar 

  13. Raehal, K.M. et al. J. Pharmacol. Exp. Ther. 314, 1195–1201 (2005).

    Article  CAS  Google Scholar 

  14. Rudd, R.A. et al. MMWR Morb. Mortal. Wkly Rep. 65, 1445–1452 (2016).

    Article  Google Scholar 

  15. Manglik, A. et al. Nature 537, 185–190 (2016).

    Article  CAS  Google Scholar 

Download references

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  1. Dyani Lewis is a freelance science journalist based in Hobart, Australia.,

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Lewis, D. Biased for benefit: Stimulating the world's most popular drug targets with more nuance. Nat Med 23, 649–651 (2017). https://doi.org/10.1038/nm0617-649

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