ArticleHuman molecular genetics2017
A flow cytometry-based screen identifies MBNL1 modulators that rescue splicing defects in myotonic dystrophy type I.
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 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Dysregulation of the MACF1-Rab14/KIF16B-FGFR Vesicular Trafficking Axis Skews MSC Lineage Commitment in Glucocorticoid-Induced Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MBNL proteins in health, disease, and therapeutic applications.Nucleic acids research · 2026Review
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Cardiac Involvement in Myotonic Dystrophy Type 1: Mechanisms, Clinical Perspectives, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Promoter-targeted small RNA duplexes increase MBNL1 transcription and mitigate myotonic dystrophy-associated spliceopathy.Nucleic acids research · 2025Article
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- On RNA-programmable gene modulation as a versatile set of principles targeting muscular dystrophies.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- The Construction of a Multi-Gene Risk Model for Colon Cancer Prognosis and Drug Treatments Prediction.International journal of molecular sciences · 2024Article
- Construction of an ER stress-related prognostic signature for predicting prognosis and screening the effective anti-tumor drug in osteosarcoma.Journal of translational medicine · 2024Article
- Mitochondrial Dysfunction in Repeat Expansion Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies.International journal of molecular sciences · 2023Review
- Vorinostat Improves Myotonic Dystrophy Type 1 Splicing Abnormalities in DM1 Muscle Cell Lines and Skeletal Muscle from a DM1 Mouse Model.International journal of molecular sciences · 2023Article
- Development of Therapeutic Approaches for Myotonic Dystrophies Type 1 and Type 2.International journal of molecular sciences · 2022Review
- Partners in crime: Proteins implicated in RNA repeat expansion diseases.Wiley interdisciplinary reviews. RNA · 2022Review
- Molecular Therapies for Myotonic Dystrophy Type 1: From Small Drugs to Gene Editing.International journal of molecular sciences · 2022Review
- Reducing the Excess Activin Signaling Rescues Muscle Degeneration in Myotonic Dystrophy Type 2Journal of personalized medicine · 2022Article
- Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy.Molecular therapy. Nucleic acids · 2021Article
- Defined D-hexapeptides bind CUG repeats and rescue phenotypes of myotonic dystrophy myotubes in a Drosophila model of the disease.Scientific reports · 2021Article
- Nanomedicine for Gene Delivery and Drug Repurposing in the Treatment of Muscular Dystrophies.Pharmaceutics · 2021Review
- Brain Pathogenesis and Potential Therapeutic Strategies in Myotonic Dystrophy Type 1.Frontiers in aging neuroscience · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Myotonic dystrophy Type 1 (DM1) is a rare genetic disease caused by the expansion of CTG trinucleotide repeats ((CTG)exp) in the 3' untranslated region of the DMPK gene. The repeat transcripts sequester the RNA binding protein Muscleblind-like protein 1 (MBNL1) and hamper its normal function in pre-mRNA splicing. Overexpressing exogenous MBNL1 in the DM1 mouse model has been shown to rescue the splicing defects and reverse myotonia. Although a viable therapeutic strategy, pharmacological modulators of MBNL1 expression have not been identified. Here, we engineered a ZsGreen tag into the endogenous MBNL1 locus in HeLa cells and established a flow cytometry-based screening system to identify compounds that increase MBNL1 level. The initial screen of small molecule compound libraries identified more than thirty hits that increased MBNL1 expression greater than double the baseline levels. Further characterization of two hits revealed that the small molecule HDAC inhibitors, ISOX and vorinostat, increased MBNL1 expression in DM1 patient-derived fibroblasts and partially rescued the splicing defect caused by (CUG)exp repeats in these cells. These findings demonstrate the feasibility of this flow-based cytometry screen to identify both small molecule compounds and druggable targets for MBNL1 upregulation.
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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.