ArticleHuman gene therapy methods2014
Adeno-associated virus-mediated overexpression of LARGE rescues α-dystroglycan function in dystrophic mice with mutations in the fukutin-related protein.
Article in Human gene therapy methods, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Treatabolome for finely targeting muscle pathology in LGMD.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Review
- Malformations of Core M3 on α-Dystroglycan Are the Leading Cause of Dystroglycanopathies.Journal of molecular neuroscience : MN · 2025Review
- Defining clinical endpoints in limb girdle muscular dystrophy: a GRASP-LGMD study.BMC neurology · 2024Article
- Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy: A GRASP-LGMD study.Research square · 2023Article
- Article
- Dystroglycanopathy: From Elucidation of Molecular and Pathological Mechanisms to Development of Treatment Methods.International journal of molecular sciences · 2021Review
- A universal gene correction approach for FKRP-associated dystroglycanopathies to enable autologous cell therapy.Cell reports · 2021Article
- Fukutin-Related Protein: From Pathology to Treatments.Trends in cell biology · 2021Review
- Human embryoid bodies as a 3D tissue model of the extracellular matrix and α-dystroglycanopathies.Disease models & mechanisms · 2020Article
- Molecular diagnosis of muscular diseases in outpatient clinics: A Canadian perspective.Neurology. Genetics · 2020Article
- biAb Mediated Restoration of the Linkage between Dystroglycan and Laminin-211 as a Therapeutic Approach for α-Dystroglycanopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- The roles of dystroglycan in the nervous system: insights from animal models of muscular dystrophy.Disease models & mechanisms · 2018Review
- LARGE expression in different types of muscular dystrophies other than dystroglycanopathy.BMC neurology · 2018Article
- Dose-Dependent Effects of FKRP Gene-Replacement Therapy on Functional Rescue and Longevity in Dystrophic Mice.Molecular therapy. Methods & clinical development · 2018Article
- Molecular Therapies for Muscular Dystrophies.Current treatment options in neurology · 2018Review
- Overexpression of Mutant FKRP Restores Functional Glycosylation and Improves Dystrophic Phenotype in FKRP Mutant Mice.Molecular therapy. Nucleic acids · 2018Article
- Genome engineering: a new approach to gene therapy for neuromuscular disorders.Nature reviews. Neurology · 2017Review
- Autologous intramuscular transplantation of engineered satellite cells induces exosome-mediated systemic expression of Fukutin-related protein and rescues disease phenotype in a murine model of limb-girdle muscular dystrophy type 2I.Human molecular genetics · 2017Article
- Efficacy of Gene Therapy Is Dependent on Disease Progression in Dystrophic Mice with Mutations in the FKRP Gene.Molecular therapy. Methods & clinical development · 2017Article
- AAV-mediated transfer of FKRP shows therapeutic efficacy in a murine model but requires control of gene expression.Human molecular genetics · 2017Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple genes (e.g., POMT1, POMT2, POMGnT1, ISPD, GTDC2, B3GALNT2, FKTN, FKRP, and LARGE) are known to be involved in the glycosylation pathway of α-dystroglycan (α-DG). Mutations of these genes result in muscular dystrophies with wide phenotypic variability. Abnormal glycosylation of α-DG with decreased extracellular ligand binding activity is a common biochemical feature of these genetic diseases. While it is known that LARGE overexpression can compensate for defects in a few aforementioned genes, it is unclear whether it can also rescue defects in FKRP function. We examined adeno-associated virus (AAV)-mediated LARGE or FKRP overexpression in two dystrophic mouse models with loss-of-function mutations: (1) Large(myd) (LARGE gene) and (2) FKRP(P448L) (FKRP gene). The results agree with previous findings that overexpression of LARGE can ameliorate the dystrophic phenotypes of Large(myd) mice. In addition, LARGE overexpression in the FKRP(P448L) mice effectively generated functional glycosylation (hyperglycosylation) of α-DG and improved dystrophic pathologies in treated muscles. Conversely, FKRP transgene overexpression failed to rescue the defect in glycosylation and improve the phenotypes of the Large(myd) mice. Our findings suggest that AAV-mediated LARGE gene therapy may still be a viable therapeutic strategy for dystroglycanopathies with FKRP deficiency.
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