Evidence map›Paper›PMID 42363603›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

Treatment with the Nox1/4 inhibitor Setanaxib ameliorates cardiac function in mouse models of Duchenne muscular dystrophy.

Rui Deng, Tabatha De Oliveira Silva, Xiang Liu, Cheng Fan, Hee Young Seok, Jingjing Wu, Ishani Wickramage, Haipeng Guo, Tian Lin, Shiju Zhang and 9 more

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Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

19 authors.

Rui DengCenter for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA.
Tabatha De Oliveira SilvaCenter for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
Xiang LiuDepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Cheng FanDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA.
Hee Young SeokDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA.
Jingjing WuCenter for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
Ishani WickramageCenter for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
Haipeng GuoDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA.
Tian LinCenter for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
Shiju ZhangCenter for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
Nihan SemerciCenter for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
Saeid TaheriDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
Yao Wei LuDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, 1 Blackfan Circle, Boston, MA 02115, USA; Department of Medicine, and Hastings Center for Pulmonary Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Zhan-Peng HuangDepartment of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA.
John D MablyCenter for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
Mingxiang TengDepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Hong ChenVascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, 1 Blackfan Circle, Boston, MA 02115, USA.
Gabriela P DinizCenter for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA. Electronic address: gabrieladiniz@usf.edu.
Da-Zhi WangCenter for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA; Department of Cardiology, Boston Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA. Electronic address: dazhiw@usf.edu.

Funding

Molecular Mechanisms Controlling Lymphatic Vascular Function in Health and DiseaseR01HL133216 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, DIXON, JAMES BRANDON · 2016 to 2025
$6.7M
Mechanisms regulating VEGF receptors in diabetic angiogenesisR01HL130845 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, XU, JIAN · 2016 to 2023
$4.9M
CD45-mediated endothelial-to-mesenchymal transition in cardiovascular diseaseR01HL141853 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, WANG, DA-ZHI · 2020 to 2023
$3.3M
Targeting Endothelial Epsins to Ameliorate Myocardial IschemiaR01HL174928 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Hong Chen, Kaifu Chen · 2024 to 2026
$2.4M
MOLECULAR MECHANISMS OF DYSTROPHIC CARDIOMYOPATHYR01HL149401 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI WANG, DA-ZHI · 2019 to 2022
$2.3M
Function and Mechanism of the Intercalated Disc Protein XinB in Cardiomyocyte Proliferation and Cardiac RegenerationR01HL168900 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI Da-Zhi Wang · 2023 to 2026
$2.2M
lncRNA Function and Mechanisms during Cardiac Development and DiseaseR01HL165794 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI Da-Zhi Wang · 2023 to 2026
$2.2M
MicroRNAs, cardiac function and cardiomyopathyR01HL138757 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI WANG, DA-ZHI · 2017 to 2020
$2.1M
CDK13 function in heart development and congenital heart diseaseR01HL177546 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI Da-Zhi Wang · 2025 to 2026
$1.4M
NHLBI NIH HHS R01 HL130845NHLBI NIH HHS R01 HL133216NHLBI NIH HHS R01 HL138757NHLBI NIH HHS R01 HL141853NHLBI NIH HHS R01 HL149401NHLBI NIH HHS R01 HL165794NHLBI NIH HHS R01 HL168900NHLBI NIH HHS R01 HL174928NHLBI NIH HHS R01 HL177546
6 · The paper itself

Abstract

Duchenne muscular dystrophy (DMD) is caused by mutations in dystrophin, leading to degeneration and weakness of skeletal and cardiac muscle. Despite great progress in the development of gene replacement therapies, DMD remains a devastating disease. In our recent work, we demonstrated that loss of the cardiac Isl1-interacting protein (CIP), which interacts with dystrophin in sarcolemma of cardiomyocytes, accelerates the progression of dystrophic cardiomyopathy and identified Nox4 as one of the downstream mediators of this process. Here, we report that setanaxib, a Nox1/4 inhibitor, protected the heart of CIP/Mdx double knockout (dKO) mice from heart failure; significantly, this compound also reduced cardiac fibrosis and protected against heart failure in Mdx/Utrn dKO mouse. At a molecular level, Nox1/4 inhibition reduced the expression of genes associated with cardiomyopathy in these animals. Further transcriptomic analysis of the hearts treated with setanaxib revealed an enrichment in genes associated with fatty acid metabolism, oxidative phosphorylation, and protein binding, while genes related to epithelial-mesenchymal transition were downregulated. Collectively, these findings suggest that oxidative stress plays a key role in development of myocardial fibrosis and heart failure caused by dystrophin deficiency and suggest that Nox1/4 inhibitor treatment could be a novel therapy to treat DMD-associated cardiomyopathy.

Indexed as

Muscular Dystrophy, DuchenneNADPH Oxidase 1NADPH Oxidase 4PyridinesAnimalsCardiomyopathiesDisease Models, AnimalDystrophinFibrosisHeart FailureHumansMiceMice, Inbred mdxMice, KnockoutMyocardiumOxidative StressDystrophinNADPH Oxidase 1NADPH Oxidase 4NOX1 protein, mouseNox4 protein, mousePyrazolonesPyridinesPyridonessetanaxibcardiomyopathyfibrosisheart failuremuscular dystrophyNox1/4 inhibitor

Identifiers

PMID42363603
PMCPMC13453391

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.