ArticleHuman gene therapy2015
Synergistic Efficacy from Gene Therapy with Coreceptor Blockade and a β2-Agonist in Murine Pompe Disease.
Article in Human gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- What's new and what's next for gene therapy in Pompe disease?Expert opinion on biological therapy · 2022Pooled it
- TRPML1 agonists synergize with enzyme replacement therapy in fibroblasts from Pompe disease patients.Journal of translational medicine · 2026Article
- Transcriptional Targeting Approaches in Cardiac Gene Transfer Using AAV Vectors.Pathogens (Basel, Switzerland) · 2023Review
- Muscle Specific Promotors for Gene Therapy - A Comparative Study in Proliferating and Differentiated Cells.Journal of neuromuscular diseases · 2023Article
- Efficacious Androgen Hormone Administration in Combination with Adeno-Associated Virus Vector-Mediated Gene Therapy in Female Mice with Pompe Disease.Human gene therapy · 2022Article
- Preclinical Research in Glycogen Storage Diseases: A Comprehensive Review of Current Animal Models.International journal of molecular sciences · 2020Review
- Comparisons of Infant and Adult Mice Reveal Age Effects for Liver Depot Gene Therapy in Pompe Disease.Molecular therapy. Methods & clinical development · 2020Article
- Advancements in AAV-mediated Gene Therapy for Pompe Disease.Journal of neuromuscular diseases · 2020Review
- Salmeterol with Liver Depot Gene Therapy Enhances the Skeletal Muscle Response in Murine Pompe Disease.Human gene therapy · 2019Article
- Bezafibrate Enhances AAV Vector-Mediated Genome Editing in Glycogen Storage Disease Type Ia.Molecular therapy. Methods & clinical development · 2019Article
- Immunosuppression overcomes insulin- and vector-specific immune responses that limit efficacy of AAV2/8-mediated insulin gene therapy in NOD mice.Gene therapy · 2019Article
- Comprehensive review of recent advances in Pompe disease: pathogenesis, management, and future directions.Frontiers in neurologyReview
- Muscle-Specific Promoters for Gene Therapy.Acta naturaeArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pompe disease (glycogen storage disease type II; acid maltase deficiency) is a devastating myopathy resulting from acid α-glucosidase (GAA) deficiency in striated and smooth muscle. Despite the availability of enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA), the limitations of ERT have prompted the preclinical development of gene therapy. Gene therapy has the advantage of continuously producing GAA, in contrast to ERT, which requires frequent injections of rhGAA. An adeno-associated viral (AAV) vector containing a muscle-specific promoter, AAV-MHCK7hGAApA, achieved high GAA expression in heart and skeletal muscle in mice with Pompe disease. However, elevated GAA activity was not sufficient to completely clear accumulated glycogen in skeletal muscle. The process of glycogen clearance from lysosomes might require improved trafficking of GAA to the lysosomes in skeletal muscle, previously achieved with the β(2)-agonist clenbuterol that enhanced glycogen clearance in skeletal muscle without increasing GAA activity. Glycogen clearance was clearly enhanced by treatment with a nondepleting anti-CD4 monoclonal antibody (anti-CD4 mAb) along with muscle-specific GAA expression in cardiac muscle, but that treatment was not effective in skeletal muscle. Furthermore, anti-CD4 mAb treatment along with clenbuterol achieved synergistic therapeutic efficacy in both cardiac and skeletal muscle. This triple therapy increased both muscle strength and weight gain. Overall, triple therapy to enhance GAA trafficking and to suppress immune responses significantly improved the efficacy of muscle-targeted gene therapy in murine Pompe disease.
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Registered trials
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.