Personalized Therapy of Hypertension: the Past and the Future

  • Paolo Manunta
  • Mara Ferrandi
  • Daniele Cusi
  • Patrizia Ferrari
  • Jan Staessen
  • Giuseppe BianchiEmail author
Novel Treatments for Hypertension (T Unger, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Novel Treatments for Hypertension


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.


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



P. Manunta’s research is supported by Ministero della Salute Italiano (RF-2011-02347356 and RF-2011-02346988) and by CVie Therapeutics Limited, Taipei.

J. Staessen’s research is currently supported by the European Union (HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-F7-305507 HOMAGE, the European Research Council Advanced Researcher Grant-2011-294713-EPLORE) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13 and G.088013).

Compliance with Ethical Standards

Conflict of Interest

Drs. Bianchi and Ferrari are consultants to CVie Therapeutic Limited, Taipei, Taiwan. Dr. Ferrendi is an employee of CVie. Dr. Manunta received research support from CVie. Drs. Cusi and Staessen declare no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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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
    Email author
  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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