ArticleHuman molecular genetics2017
AAV-mediated transfer of FKRP shows therapeutic efficacy in a murine model but requires control of gene expression.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 43 citations in OpenAlex.
- Defining Haplosufficiency in Autosomal Recessive Limb-Girdle Muscular Dystrophy Using Molecular Markers in Disease Carriers.Neurology. Genetics · 2026Article
- Bridging science and hope: the evolving story of gene therapy for neuromuscular diseases.Frontiers in cell and developmental biology · 2026Review
- Biosynthesis and Regulation of Laminin-Binding O-Mannosyl Glycans Related to Muscular Dystrophy.Advances in experimental medicine and biology · 2026Review
- Current clinical applications of AAV-mediated gene therapy.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
- Malformations of Core M3 on α-Dystroglycan Are the Leading Cause of Dystroglycanopathies.Journal of molecular neuroscience : MN · 2025Review
- Prospective observational study of FKRP-related limb-girdle muscular dystrophy R9: A GRASP consortium study.Annals of clinical and translational neurology · 2025Observational
- Dual FKRP/FST gene therapy normalizes ambulation, increases strength, decreases pathology, and amplifies gene expression in LGMDR9 mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Molecular mechanisms and therapeutic strategies for neuromuscular diseases.Cellular and molecular life sciences : CMLS · 2024Review
- Defining clinical endpoints in limb girdle muscular dystrophy: a GRASP-LGMD study.BMC neurology · 2024Article
- Break Down of the Complexity and Inconsistency Between Levels of Matriglycan and Disease Phenotype in FKRP-Related Dystroglycanopathies: A Review and Model of Interpretation.Journal of neuromuscular diseases · 2024Review
- Article
- Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy: A GRASP-LGMD study.Research square · 2023Article
- Efficacy and muscle safety assessment of fukutin-related protein gene therapy.Molecular therapy. Methods & clinical development · 2023Article
- Congenital disorders of glycosylation: narration of a story through its patents.Orphanet journal of rare diseases · 2023Review
- Current Strategies of Muscular Dystrophy Therapeutics: An Overview.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Compound HeterozygousInternational journal of molecular sciences · 2022Article
- 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
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Limb Girdle Muscular Dystrophies type 2I (LGMD2I), a recessive autosomal muscular dystrophy, is caused by mutations in the Fukutin Related Protein (FKRP) gene. It has been proposed that FKRP, a ribitol-5-phosphate transferase, is a participant in α-dystroglycan (αDG) glycosylation, which is important to ensure the cell/matrix anchor of muscle fibers. A LGMD2I knock-in mouse model was generated to express the most frequent mutation (L276I) encountered in patients. The expression of FKRP was not altered neither at transcriptional nor at translational levels, but its function was impacted since abnormal glycosylation of αDG was observed. Skeletal muscles were functionally impaired from 2 months of age and a moderate dystrophic pattern was evident starting from 6 months of age. Gene transfer with a rAAV2/9 vector expressing Fkrp restored biochemical defects, corrected the histological abnormalities and improved the resistance to eccentric stress in the mouse model. However, injection of high doses of the vector induced a decrease of αDG glycosylation and laminin binding, even in WT animals. Finally, intravenous injection of the rAAV-Fkrp vector into a dystroglycanopathy mouse model due to Fukutin (Fktn) knock-out indicated a dose-dependent toxicity. These data suggest requirement for a control of FKRP expression in muscles.
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