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RESEARCH PRODUCT
Myotonic dystrophy: candidate small molecule therapeutics
Piotr KoniecznyJuan M. Fernandez-costaManuel Pérez-alonsoAnna S. RapisardaEstela Selma-sorianoRuben Arterosubject
musculoskeletal diseases0301 basic medicineTherapeutic gene modulationcongenital hereditary and neonatal diseases and abnormalitiesMutantComputational biologyBiologyMyotonic dystrophyMyotonin-Protein Kinase03 medical and health sciences0302 clinical medicineTrinucleotide RepeatsDrug DiscoveryGene expressionmedicineAnimalsHumansMyotonic DystrophyGenePharmacologyRegulation of gene expressionGeneticsDrug RepositioningRational designmedicine.diseaseSmall moleculeHigh-Throughput Screening Assays030104 developmental biologyGene Expression RegulationDrug Design030217 neurology & neurosurgerydescription
Myotonic dystrophy type 1 (DM1) is a rare multisystemic neuromuscular disorder caused by expansion of CTG trinucleotide repeats in the noncoding region of the DMPK gene. Mutant DMPK transcripts are toxic and alter gene expression at several levels. Chiefly, the secondary structure formed by CUGs has a strong propensity to capture and retain proteins, like those of the muscleblind-like (MBNL) family. Sequestered MBNL proteins cannot then fulfill their normal functions. Many therapeutic approaches have been explored to reverse these pathological consequences. Here, we review the myriad of small molecules that have been proposed for DM1, including examples obtained from computational rational design, HTS, drug repurposing, and therapeutic gene modulation.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-03-21 | Drug Discovery Today |