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Preclinical development of a miR-132 inhibitor for heart failure treatment

Research output: Contribution to journalArticle

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Preclinical development of a miR-132 inhibitor for heart failure treatment. / Foinquinos, Ariana; Batkai, Sandor; Genschel, Celina; Viereck, Janika; Rump, Steffen; Gyöngyösi, Mariann; Traxler, Denise; Riesenhuber, Martin; Spannbauer, Andreas; Lukovic, Dominika; Weber, Natalie; Zlabinger, Katrin; Hašimbegović, Ena; Winkler, Johannes; Fiedler, Jan; Dangwal, Seema; Fischer, Martin; Roche, Jeanne de la; Wojciechowski, Daniel; Kraft, Theresia; Garamvölgyi, Rita; Neitzel, Sonja; Chatterjee, Shambhabi; Yin, Xiaoke; Bär, Christian; Mayr, Manuel; Xiao, Ke; Thum, Thomas.

In: Nature Communications, Vol. 11, No. 1, 633, 01.12.2020.

Research output: Contribution to journalArticle

Harvard

Foinquinos, A, Batkai, S, Genschel, C, Viereck, J, Rump, S, Gyöngyösi, M, Traxler, D, Riesenhuber, M, Spannbauer, A, Lukovic, D, Weber, N, Zlabinger, K, Hašimbegović, E, Winkler, J, Fiedler, J, Dangwal, S, Fischer, M, Roche, JDL, Wojciechowski, D, Kraft, T, Garamvölgyi, R, Neitzel, S, Chatterjee, S, Yin, X, Bär, C, Mayr, M, Xiao, K & Thum, T 2020, 'Preclinical development of a miR-132 inhibitor for heart failure treatment', Nature Communications, vol. 11, no. 1, 633. https://doi.org/10.1038/s41467-020-14349-2

APA

Foinquinos, A., Batkai, S., Genschel, C., Viereck, J., Rump, S., Gyöngyösi, M., ... Thum, T. (2020). Preclinical development of a miR-132 inhibitor for heart failure treatment. Nature Communications, 11(1), [633]. https://doi.org/10.1038/s41467-020-14349-2

Vancouver

Foinquinos A, Batkai S, Genschel C, Viereck J, Rump S, Gyöngyösi M et al. Preclinical development of a miR-132 inhibitor for heart failure treatment. Nature Communications. 2020 Dec 1;11(1). 633. https://doi.org/10.1038/s41467-020-14349-2

Author

Foinquinos, Ariana ; Batkai, Sandor ; Genschel, Celina ; Viereck, Janika ; Rump, Steffen ; Gyöngyösi, Mariann ; Traxler, Denise ; Riesenhuber, Martin ; Spannbauer, Andreas ; Lukovic, Dominika ; Weber, Natalie ; Zlabinger, Katrin ; Hašimbegović, Ena ; Winkler, Johannes ; Fiedler, Jan ; Dangwal, Seema ; Fischer, Martin ; Roche, Jeanne de la ; Wojciechowski, Daniel ; Kraft, Theresia ; Garamvölgyi, Rita ; Neitzel, Sonja ; Chatterjee, Shambhabi ; Yin, Xiaoke ; Bär, Christian ; Mayr, Manuel ; Xiao, Ke ; Thum, Thomas. / Preclinical development of a miR-132 inhibitor for heart failure treatment. In: Nature Communications. 2020 ; Vol. 11, No. 1.

Bibtex Download

@article{08a44eafa664418c8b97a004311fc04e,
title = "Preclinical development of a miR-132 inhibitor for heart failure treatment",
abstract = "Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression. We previously demonstrated that miR-132 is both necessary and sufficient to drive the pathological cardiomyocytes growth, a hallmark of adverse cardiac remodelling. Therefore, miR-132 may serve as a target for HF therapy. Here we report further mechanistic insight of the mode of action and translational evidence for an optimized, synthetic locked nucleic acid antisense oligonucleotide inhibitor (antimiR-132). We reveal the compound’s therapeutic efficacy in various models, including a clinically highly relevant pig model of HF. We demonstrate favourable pharmacokinetics, safety, tolerability, dose-dependent PK/PD relationships and high clinical potential for the antimiR-132 treatment scheme.",
author = "Ariana Foinquinos and Sandor Batkai and Celina Genschel and Janika Viereck and Steffen Rump and Mariann Gy{\"o}ngy{\"o}si and Denise Traxler and Martin Riesenhuber and Andreas Spannbauer and Dominika Lukovic and Natalie Weber and Katrin Zlabinger and Ena Hašimbegović and Johannes Winkler and Jan Fiedler and Seema Dangwal and Martin Fischer and Roche, {Jeanne de la} and Daniel Wojciechowski and Theresia Kraft and Rita Garamv{\"o}lgyi and Sonja Neitzel and Shambhabi Chatterjee and Xiaoke Yin and Christian B{\"a}r and Manuel Mayr and Ke Xiao and Thomas Thum",
year = "2020",
month = "12",
day = "1",
doi = "10.1038/s41467-020-14349-2",
language = "English",
volume = "11",
journal = "Nat Commun",
issn = "2041-1723",
number = "1",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Preclinical development of a miR-132 inhibitor for heart failure treatment

AU - Foinquinos, Ariana

AU - Batkai, Sandor

AU - Genschel, Celina

AU - Viereck, Janika

AU - Rump, Steffen

AU - Gyöngyösi, Mariann

AU - Traxler, Denise

AU - Riesenhuber, Martin

AU - Spannbauer, Andreas

AU - Lukovic, Dominika

AU - Weber, Natalie

AU - Zlabinger, Katrin

AU - Hašimbegović, Ena

AU - Winkler, Johannes

AU - Fiedler, Jan

AU - Dangwal, Seema

AU - Fischer, Martin

AU - Roche, Jeanne de la

AU - Wojciechowski, Daniel

AU - Kraft, Theresia

AU - Garamvölgyi, Rita

AU - Neitzel, Sonja

AU - Chatterjee, Shambhabi

AU - Yin, Xiaoke

AU - Bär, Christian

AU - Mayr, Manuel

AU - Xiao, Ke

AU - Thum, Thomas

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression. We previously demonstrated that miR-132 is both necessary and sufficient to drive the pathological cardiomyocytes growth, a hallmark of adverse cardiac remodelling. Therefore, miR-132 may serve as a target for HF therapy. Here we report further mechanistic insight of the mode of action and translational evidence for an optimized, synthetic locked nucleic acid antisense oligonucleotide inhibitor (antimiR-132). We reveal the compound’s therapeutic efficacy in various models, including a clinically highly relevant pig model of HF. We demonstrate favourable pharmacokinetics, safety, tolerability, dose-dependent PK/PD relationships and high clinical potential for the antimiR-132 treatment scheme.

AB - Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression. We previously demonstrated that miR-132 is both necessary and sufficient to drive the pathological cardiomyocytes growth, a hallmark of adverse cardiac remodelling. Therefore, miR-132 may serve as a target for HF therapy. Here we report further mechanistic insight of the mode of action and translational evidence for an optimized, synthetic locked nucleic acid antisense oligonucleotide inhibitor (antimiR-132). We reveal the compound’s therapeutic efficacy in various models, including a clinically highly relevant pig model of HF. We demonstrate favourable pharmacokinetics, safety, tolerability, dose-dependent PK/PD relationships and high clinical potential for the antimiR-132 treatment scheme.

UR - http://www.scopus.com/inward/record.url?scp=85078827680&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-14349-2

DO - 10.1038/s41467-020-14349-2

M3 - Article

C2 - 32005803

AN - SCOPUS:85078827680

VL - 11

JO - Nat Commun

JF - Nat Commun

SN - 2041-1723

IS - 1

M1 - 633

ER -

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