ArticleGene therapy2016
β-Sarcoglycan gene transfer decreases fibrosis and restores force in LGMD2E mice.
Article in Gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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
26 citing papers in PubMed, 35 citations in OpenAlex.
- Gene therapy with bidridistrogene xeboparvovec for limb-girdle muscular dystrophy type 2E/R4: phase 1/2 trial results.Nature medicine · 2024Trial
- Targeting muscle fibrosis using non-specific collagenase injections destabilizes the basal lamina and induces matrix remodeling.Skeletal muscle · 2026Article
- Genetic Deletion of the Purinergic ReceptorACS pharmacology & translational science · 2025Article
- Sarcospan protects against LGMD R5 via remodeling of the sarcoglycan complex composition in dystrophic mice.The Journal of clinical investigation · 2025Article
- Current clinical applications of AAV-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Review
- Sarcoglycans are enriched at the neuromuscular junction in a nerve-dependent manner.Cell death & disease · 2025Article
- Thrombospondin-4 deletion does not exacerbate muscular dystrophy in β-sarcoglycan-deficient and laminin α2 chain-deficient mice.Scientific reports · 2024Article
- Use of plasmapheresis to lower anti-AAV antibodies in nonhuman primates with pre-existing immunity to AAVrh74.Molecular therapy. Methods & clinical development · 2024Article
- Expression and function of four AAV-based constructs for dystrophin restoration in the mdx mouse model of Duchenne muscular dystrophy.Biology open · 2023Article
- [Molecular therapies: present and future in neuromuscular diseases].Der Nervenarzt · 2023Review
- Systemic γ-sarcoglycan AAV gene transfer results in dose-dependent correction of muscle deficits in the LGMD 2C/R5 mouse model.Molecular therapy. Methods & clinical development · 2023Article
- P2X7 Receptor Antagonist Reduces Fibrosis and Inflammation in a Mouse Model of Alpha-Sarcoglycan Muscular Dystrophy.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Dose-Escalation Study of Systemically Delivered rAAVrh74.MHCK7.micro-dystrophin in theHuman gene therapy · 2021Article
- Preclinical Systemic Delivery of Adeno-Associated α-Sarcoglycan Gene Transfer for Limb-Girdle Muscular Dystrophy.Human gene therapy · 2021Article
- Muscle Diversity, Heterogeneity, and Gradients: Learning from Sarcoglycanopathies.International journal of molecular sciences · 2021Review
- The ties that bind: functional clusters in limb-girdle muscular dystrophy.Skeletal muscle · 2020Review
- Adeno-Associated Virus-Mediated Delivery of CRISPR for Cardiac Gene Editing in Mice.Journal of visualized experiments : JoVE · 2018Article
- Molecular Therapies for Muscular Dystrophies.Current treatment options in neurology · 2018Review
- Impaired regeneration in calpain-3 null muscle is associated with perturbations in mTORC1 signaling and defective mitochondrial biogenesis.Skeletal muscle · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Limb-girdle muscular dystrophy type 2E (LGMD2E) results from mutations in the β-sarcoglycan (SGCB) gene causing loss of functional protein and concomitant loss of dystrophin-associated proteins. The disease phenotype is characterized by muscle weakness and wasting, and dystrophic features including muscle fiber necrosis, inflammation and fibrosis. The Sgcb-null mouse recapitulates the clinical phenotype with significant endomysial fibrosis providing a relevant model to test whether gene replacement will be efficacious. We directly addressed this question using a codon optimized human β-sarcoglycan gene (hSGCB) driven by a muscle-specific tMCK promoter (scAAVrh74.tMCK.hSGCB). Following isolated limb delivery (5 × 10(11) vector genome (vg)), 91.2% of muscle fibers in the lower limb expressed β-sarcoglycan, restoring assembly of the sarcoglycan complex and protecting the membrane from Evans blue dye leakage. Histological outcomes were significantly improved including decreased central nucleation, normalization of muscle fiber size, decreased macrophages and inflammatory mononuclear cells, and an average of a 43% reduction in collagen deposition in treated muscle compared with untreated muscle at end point. These measures correlated with improvement of tetanic force and resistance to eccentric contraction. In 6-month-old mice, as indicated by collagen staining, scAAVrh74.tMCK.hSGCB treatment reduced fibrosis by 42%. This study demonstrates the potential for gene replacement to reverse debilitating fibrosis, typical of muscular dystrophy, thereby providing compelling evidence for movement to clinical gene replacement for LGMD2E.
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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.