Trial reportAnnals of neurology2010
Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D.
Trial report in Annals of neurology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 141 papers, 2 of them syntheses that pooled 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.
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.
Phase I Gene Transfer of rAAV1.tMCK.Human-alpha-sarcoglycan for Limb Girdle Muscular Dystrophy Type 2D (LGMD2D)
Phase I/IIA Gene Transfer Clinical Trial for LGMD2D (Alpha-Sarcoglycan Deficiency) Using scAAVrh74.tMCK.hSGCA
Phase I/IIa Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.GALGT2
Long-Term Development of Muscular Dystrophy Outcome Assessments (GRASP-01-005)
Who cites it
141 citing papers in PubMed, 2 syntheses or guidelines pooled it, 240 citations in OpenAlex.
- Incidence, timing, and clinical significance of adverse immune events after gene replacement therapy: A systematic review and meta-analysis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Progression to Loss of Ambulation Among Patients with Autosomal Recessive Limb-girdle Muscular Dystrophy: A Systematic Review.Journal of neuromuscular diseases · 2022Pooled it
- Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for α-1-antitrypsin deficiency.Proceedings of the National Academy of Sciences of the United States of America · 2017Trial
- Prevalence of AAV1 neutralizing antibodies and consequences for a clinical trial of gene transfer for advanced heart failure.Gene therapy · 2016Trial
- A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Trial
- Phase I/II trial of adeno-associated virus-mediated alpha-glucosidase gene therapy to the diaphragm for chronic respiratory failure in Pompe disease: initial safety and ventilatory outcomes.Human gene therapy · 2013Trial
- Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Trial
- Defining Haplosufficiency in Autosomal Recessive Limb-Girdle Muscular Dystrophy Using Molecular Markers in Disease Carriers.Neurology. Genetics · 2026Article
- Overcoming host immune responses to an AAV-delivered HIV-1 bNAb in rhesus macaques mediated by co-delivery of PD-L1.bioRxiv : the preprint server for biology · 2026Article
- Co-delivered PD-L1 rescues the protective efficacy mediated by an AAV-expressed HIV-1 bNAb.bioRxiv : the preprint server for biology · 2026Article
- The co-delivery of Programmed Death 1 ligands enhances and prolongs rAAV-mediated gene expression in pre-immunized mice.Gene therapy · 2026Article
- Bridging science and hope: the evolving story of gene therapy for neuromuscular diseases.Frontiers in cell and developmental biology · 2026Review
- Limb-Girdle Muscular Dystrophy Scientific Workshop: A Multistakeholder Discussion Focused on Charting the Path Forward for Drug Development.Neurology. Clinical practice · 2025Review
- Sarcoglycanopathies: From clinical diagnosis to new promising therapies.Journal of neuromuscular diseases · 2025Review
- Current clinical applications of AAV-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The road toward AAV-mediated gene therapy of Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Treatabolome for finely targeting muscle pathology in LGMD.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Review
- Long-Term Survival and Myocardial Function Following Systemic Delivery of Delandistrogene Moxeparvovec in DMDHuman gene therapy · 2024Article
- Redundancy in Innate Immune Pathways That Promote CD8Viruses · 2024Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThe aim of this study was to attain long-lasting alpha-sarcoglycan gene expression in limb-girdle muscular dystrophy, type 2D (LGMD2D) subjects mediated by adeno-associated virus (AAV) gene transfer under control of a muscle specific promoter (tMCK).
methodsrAAV1.tMCK.hSGCA (3.25 × 10¹¹ vector genomes) was delivered to the extensor digitorum brevis muscle of 3 subjects with documented SGCA mutations via a double-blind, randomized, placebo controlled trial. Control sides received saline. The blind was not broken until the study was completed at 6 months and all results were reported to the oversight committee.
resultsPersistent alpha-sarcoglycan gene expression was achieved for 6 months in 2 of 3 LGMD2D subjects. Markers for muscle fiber transduction other than alpha-sarcoglycan included expression of major histocompatibility complex I, increase in muscle fiber size, and restoration of the full sarcoglycan complex. Mononuclear inflammatory cells recruited to the site of gene transfer appeared to undergo programmed cell death, demonstrated by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling and caspase-3 staining. A patient failing gene transfer demonstrated an early rise in neutralizing antibody titers and T-cell immunity to AAV, validated by enzyme-linked immunospot on the second day after gene injection. This was in clear distinction to other participants with satisfactory gene expression.
interpretationThe findings of this gene replacement study in LGMD2D subjects have important implications not previously demonstrated in muscular dystrophy. Long-term, sustainable gene expression of alpha-sarcoglycan was observed following gene transfer mediated by AAV. The merit of a muscle-specific tMCK promoter, not previously used in a clinical trial, was evident, and the potential for reversal of disease was displayed.
Indexed as
Identifiers
What OpenQuestion holds
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.