Personalized Therapy of Hypertension: the Past and the Future

  • Paolo Manunta
  • Mara Ferrandi
  • Daniele Cusi
  • Patrizia Ferrari
  • Jan Staessen
  • Giuseppe Bianchi
Novel Treatments for Hypertension (T Unger, Section Editor)

DOI: 10.1007/s11906-016-0632-y

Cite this article as:
Manunta, P., Ferrandi, M., Cusi, D. et al. Curr Hypertens Rep (2016) 18: 24. doi:10.1007/s11906-016-0632-y
Part of the following topical collections:
  1. Topical Collection on Novel Treatments for Hypertension

Abstract

During the past 20 years, the studies on genetics or pharmacogenomics of primary hypertension provided interesting results supporting the role of genetics, but no actionable finding ready to be translated into personalized medicine. Two types of approaches have been applied: a “hypothesis-driven” approach on the candidate genes, coding for proteins involved in the biochemical machinery underlying the regulation of BP, and an “unbiased hypothesis-free” approach with GWAS, based on the randomness principles of frequentist statistics. During the past 10–15 years, the application of the latter has overtaken the application of the former leading to an enlargement of the number of previously unknown candidate loci or genes but without any actionable result for the therapy of hypertension. In the present review, we summarize the results of our hypothesis-driven approach based on studies carried out in rats with genetic hypertension and in humans with essential hypertension at the pre-hypertensive and early hypertensive stages. These studies led to the identification of mutant adducin and endogenous ouabain as candidate genetic-molecular mechanisms in both species. Rostafuroxin has been developed for its ability to selectively correct Na+ pump abnormalities sustained by the two abovementioned mechanisms and to selectively reduce BP in rats and in humans carrying the gene variants underlying the mutant adducin and endogenous ouabain (EO) effects. A clinical trial is ongoing to substantiate these findings. Future studies should apply both the candidate gene and GWAS approaches to fully exploit the potential of genetics in optimizing the personalized therapy.

Keywords

Hypertension Genetics Candidate gene GWAS Personalized therapy Adducin Endogenous ouabain Rostafuroxin Pharmacogenomics Kidney cross-transplantation 

Funding information

Funder NameGrant NumberFunding Note
Ministero della Salute Italiano
  • RF-2011-02347356 and RF-2011-02346988
European Union
  • HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-F7-305507 HOMAGE
European Research Council Advanced Researcher
  • Grant-2011-294713-EPLORE
Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium
  • G.0881.13 and G.088013

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Paolo Manunta
    • 1
  • Mara Ferrandi
    • 2
  • Daniele Cusi
    • 3
  • Patrizia Ferrari
    • 2
  • Jan Staessen
    • 4
    • 5
  • Giuseppe Bianchi
    • 1
    • 2
  1. 1.Università Vita Salute San Raffaele, Chair of Nephrology; IRCCS San Raffaele Scientific Institute, Genomics of Renal Disease and Hypertension UnitMilanItaly
  2. 2.CVie Therapeutics LimitedTaipeiTaiwan
  3. 3.Italian National Centre of ResearchInstitute of Biomedical TechnologiesSegrateItaly
  4. 4.Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular SciencesUniversity of LeuvenLeuvenBelgium
  5. 5.R&D Group VitaKMaastricht UniversityMaastrichtThe Netherlands

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