ArticleEMBO reports2019
A new patient-derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of α-dystroglycan.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Engineered human myogenic cells in hydrogels generate innervated vascularized myofibers within dystrophic mouse muscle on long-term engraftment.Cell reports. Medicine · 2025Article
- Malformations of Core M3 on α-Dystroglycan Are the Leading Cause of Dystroglycanopathies.Journal of molecular neuroscience : MN · 2025Review
- Novel Radiological Brain Anomalies in a Patient with Congenital Muscular Dystrophy due to FKRP Mexican Founder Mutation c.1387A > G: Review of the Literature.Journal of pediatric genetics · 2023Article
- Dystroglycanopathy: From Elucidation of Molecular and Pathological Mechanisms to Development of Treatment Methods.International journal of molecular sciences · 2021Review
- Optogenetic modeling of human neuromuscular circuits in Duchenne muscular dystrophy with CRISPR and pharmacological corrections.Science advances · 2021Article
- High degree of conservation of the enzymes synthesizing the laminin-binding glycoepitope of α-dystroglycan.Open biology · 2021Article
- Fukutin-Related Protein: From Pathology to Treatments.Trends in cell biology · 2021Review
- The use of induced pluripotent stem cells in domestic animals: a narrative review.BMC veterinary research · 2020Review
- Mice carrying an analogous heterozygous dynamin 2 K562E mutation that causes neuropathy in humans develop predominant characteristics of a primary myopathy.Human molecular genetics · 2020Article
- The Challenge of Bringing iPSCs to the Patient.International journal of molecular sciences · 2019Review
- A new patient-derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of α-dystroglycan.EMBO reports · 2019Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
Dystroglycan, an extracellular matrix receptor, has essential functions in various tissues. Loss of α-dystroglycan-laminin interaction due to defective glycosylation of α-dystroglycan underlies a group of congenital muscular dystrophies often associated with brain malformations, referred to as dystroglycanopathies. The lack of isogenic human dystroglycanopathy cell models has limited our ability to test potential drugs in a human- and neural-specific context. Here, we generated induced pluripotent stem cells (iPSCs) from a severe dystroglycanopathy patient with homozygous FKRP (fukutin-related protein gene) mutation. We showed that CRISPR/Cas9-mediated gene correction of FKRP restored glycosylation of α-dystroglycan in iPSC-derived cortical neurons, whereas targeted gene mutation of FKRP in wild-type cells disrupted this glycosylation. In parallel, we screened 31,954 small molecule compounds using a mouse myoblast line for increased glycosylation of α-dystroglycan. Using human FKRP-iPSC-derived neural cells for hit validation, we demonstrated that compound 4-(4-bromophenyl)-6-ethylsulfanyl-2-oxo-3,4-dihydro-1H-pyridine-5-carbonitrile (4BPPNit) significantly augmented glycosylation of α-dystroglycan, in part through upregulation of LARGE1 glycosyltransferase gene expression. Together, isogenic human iPSC-derived cells represent a valuable platform for facilitating dystroglycanopathy drug discovery and therapeutic development.
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Registered trials
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