Evidence map›Paper›PMID 40148575›Full record

ArticleCommunications medicine2025

AAV9-cBIN1 gene therapy rescues chronic heart failure due to ischemic cardiomyopathy in a canine model.

Muhammad S Khan, Douglas Smego, Jing Li, Yuki Ishidoya, Emmanuel Offei, Martha Sofia Ruiz Castillo, Annie M Hirahara, Pia Balmaceda, Jennifer Hunter, Anand Athavale and 7 more

Abstract read
In one paragraph

Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Review
  2. Article
  3. Past, Present and Future of Regenerative Gene Therapy for Ischemic Heart Failure.Journal of cardiovascular translational research · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Muhammad S KhanNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.ORCID http://orcid.org/0000-0002-6232-2633
Douglas SmegoDepartment of Surgery, Division of Cardiothoracic Surgery, University of Utah, Salt Lake City, UT, 84112, USA.
Jing LiNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Yuki IshidoyaNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.ORCID http://orcid.org/0000-0003-2825-8479
Emmanuel OffeiNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Martha Sofia Ruiz CastilloNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Annie M HiraharaNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Pia BalmacedaNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Jennifer HunterNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Anand AthavaleNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Monica P ReveloDepartment of Pathology, University of Utah, Salt Lake City, UT, 84112, USA.
Joseph A PalatinusNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Craig H SelzmanNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Ravi RanjanNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.
TingTing HongNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA.ORCID http://orcid.org/0000-0002-0243-5046
Derek J DosdallNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA. Derek.Dosdall@utah.edu.ORCID http://orcid.org/0000-0001-5059-6824
Robin M ShawNora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, 84112, USA. Robin.Shaw@hsc.utah.edu.ORCID http://orcid.org/0000-0001-7429-6092

Funding

TRAINING IN CARDIOVASCULAR RESEARCHT32HL007576 · NHLBI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Stavros George Drakos, Robin M Shaw · 1985 to 2026
$10.6M
His-Purkinje Pacing for Low Energy Implantable Cardioverter DefibrillatorsR01HL128752 · NHLBI · UNIVERSITY OF UTAH · PI DOSDALL, DEREK J · 2015 to 2024
$5.0M
Correcting Cardiac Microdomains Reverses Non-Ischemic CardiomyopathyR01HL170196 · NHLBI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI TingTing Hong, Robin M Shaw · 2023 to 2026
$2.5M
Regulation of Cav1.2 Trafficking by GJA1-20k and cBIN1R01HL159983 · NHLBI · UNIVERSITY OF UTAH · PI HONG, TINGTING, SHAW, ROBIN M · 2021 to 2024
$2.2M
Novel Gene Therapy For Chronic Ischemic Heart FailureR01HL171686 · NHLBI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Derek J Dosdall, Robin M Shaw · 2024 to 2026
$2.2M
Unlocking Trafficking Specificity for Cx43 Gap JunctionsR01HL152691 · NHLBI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Robin M Shaw · 2020 to 2026
$2.0M
Novel lead for selective His bundle sensing and low-threshold pacingR21HL156039 · NHLBI · UNIVERSITY OF UTAH · PI DOSDALL, DEREK J · 2021 to 2022
$419k
American Heart Association (American Heart Association, Inc.) 23CDA1057448NHLBI NIH HHS R01 HL128752NHLBI NIH HHS R01 HL159983NHLBI NIH HHS R01 HL171686NHLBI NIH HHS R21 HL156039NHLBI NIH HHS T32 HL007576U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL128752U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL152691U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL159983U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL170196U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL171686U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R21HL156039
6 · The paper itself

Abstract

backgroundIschemic cardiomyopathy and resultant heart failure (HF) is a significant cause of morbidity and mortality worldwide. Downregulation of cardiac bridging integrator 1 (cBIN1), a membrane scaffolding protein responsible for organizing t-tubules and organizing the calcium handing apparatus, occurs in progressive HF. Therefore, gene therapy upregulating cBIN1 production may rescue failing muscle and clinical HF.

methodsAdult mongrel dogs underwent ligation of the left anterior descending artery and developed progressive dilated cardiomyopathy and chronic HF. When left ventricular ejection fraction (LVEF) dropped below 40%, the animals received a one-time series of endocardial injections of either of low dose gene therapy composed of either adeno-associated virus serotype 9 packaged cBIN1 (AAV9-cBIN1, n = 6) or AAV9-GFP (green fluorescent protein, n = 4). Animals were followed up to 7 weeks after therapy delivery with laboratory, echocardiography, and endocardial mapping assessment.

resultsPost injection of the negative control, animals develop progressive symptomatic HF requiring early termination of all but one animal prior to the end of the study. In contrast, the AAV9-cBIN1-treated group reveals a significant improvement in LV function, with a noticeable improvement in LVEF (29 ± 3% vs. 42 ± 2%, p = 0.0095) and global longitudinal strain (-7.1 ± 0.9% vs. -12.5 ± 1.6%, p = 0.0095). Compared to the control animals, the AAV9-cBIN1-treated group displays improved T-tubule morphology, left ventricular chamber size, plasma biomarkers, and endocardial voltage, and survives the study period.

conclusionsChronic HF from ischemic cardiomyopathy can be successfully treated with low dose AAV9-cBIN1 gene therapy. This study indicates that myocardial specific therapy can dramatically reverse HF progression.

Identifiers

PMID40148575
PMCPMC11950290

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.