Evidence map›Paper›PMID 40671677›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

AAV-microutrophin gene therapy confers durable cardioprotection against pharmacologic and exercise-induced injury in the mdx mouse.

Coral M Kasden, Maria P Corzo, Christopher D Greer, Tanvi Singh, Rufranshell Reyes, Alaine Castillo, Zoltan Arany, Benjamin W Kozyak, Hansell H Stedman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

9 authors.

Coral M KasdenDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Program, Biomedical Graduate Studies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Maria P CorzoDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Christopher D GreerDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Program, Biomedical Graduate Studies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Tanvi SinghDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Rufranshell ReyesDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Alaine CastilloDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Zoltan AranyCell and Molecular Biology Graduate Program, Biomedical Graduate Studies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Benjamin W KozyakCardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Anesthesiology & Critical Care Medicine, The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Cardiac Critical Care Medicine, The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Hansell H StedmanDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Program, Biomedical Graduate Studies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: hstedman@pennmedicine.upenn.edu.

Funding

IND-enabling studies of non-immunogenic gene therapy for ultra-rare DMD patients excluded from dystrophin trialsU01NS134672 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI HANSELL H STEDMAN · 2024 to 2026
$7.3M
Training in Muscle Biology and Muscle DiseaseT32AR053461 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI OSTAP, E. MICHAEL · 2006 to 2025
$4.9M
NIAMS NIH HHS T32 AR053461NINDS NIH HHS U01 NS134672
6 · The paper itself

Abstract

Duchenne muscular dystrophy (DMD) is the most common childhood-onset muscle degenerative disease, caused by genetic deficiency of dystrophin, resulting in premature death due to cardiorespiratory failure. Gene therapy clinical trials employing adeno-associated virus (AAV) systemically delivering miniaturized dystrophin have provided mixed results with lingering concerns about safety, long-term efficacy, and the absence of information about cardiac protection. AAV-microutrophin (AAV-μUtro) represents an attractive alternative, previously shown in pre-clinical models to rescue skeletal muscle disease without stimulating an immune response to transgene product. It remains untested whether AAV-μUtro is protective in the dystrophic heart, in part due to limitations in DMD cardiomyopathy models. Here, we present reproducible pharmacologic- and exercise-induced cardiac injury models in the mdx mouse and rigorous testing of AAV-μUtro for efficacy and durability. AAV-μUtro was highly protective against cardiac injury in these distinct models, evidenced by reduced cardiac troponin I levels and Evans blue dye uptake compared to untreated mdx mice. AAV-μUtro improved running performance following a cardiac stressor and prevented maladaptive cardiac remodeling in response to daily running 10 months post-treatment. These results demonstrate AAV-μUtro's durable cardioprotection during cardiac stress and daily physical activity and are promising with respect to meaningful amelioration of cardiac disease in children with DMD.

Indexed as

DependovirusGenetic TherapyGenetic VectorsMuscular Dystrophy, DuchenneUtrophinAnimalsCardiomyopathiesDisease Models, AnimalDystrophinHumansMaleMiceMice, Inbred mdxMyocardiumPhysical Conditioning, AnimalDystrophinUtrophinAAVcardiomyopathyDuchenne muscular dystrophydystrophingene therapyutrophin

Identifiers

PMID40671677
PMCPMC12848168

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.