{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:47:24Z","timestamp":1780516044957,"version":"3.54.1"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AM from Genome Canada","award":["400349"],"award-info":[{"award-number":["400349"]}]},{"name":"AM from Genome Canada","award":["OGI-049"],"award-info":[{"award-number":["OGI-049"]}]},{"name":"Canadian Institutes of Health Research","award":["400349"],"award-info":[{"award-number":["400349"]}]},{"name":"Canadian Institutes of Health Research","award":["OGI-049"],"award-info":[{"award-number":["OGI-049"]}]},{"name":"Ontario Genomics","award":["400349"],"award-info":[{"award-number":["400349"]}]},{"name":"Ontario Genomics","award":["OGI-049"],"award-info":[{"award-number":["OGI-049"]}]},{"name":"Children\u2019s Hospital of Eastern Ontario (CHEO) Foundation","award":["400349"],"award-info":[{"award-number":["400349"]}]},{"name":"Children\u2019s Hospital of Eastern Ontario (CHEO) Foundation","award":["OGI-049"],"award-info":[{"award-number":["OGI-049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myotonic dystrophy type 1 (DM1), the most common form of adult muscular dystrophy, is caused by an abnormal expansion of CTG repeats in the 3\u2032 untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The expanded repeats of the DMPK mRNA form hairpin structures in vitro, which cause misregulation and\/or sequestration of proteins including the splicing regulator muscleblind-like 1 (MBNL1). In turn, misregulation and sequestration of such proteins result in the aberrant alternative splicing of diverse mRNAs and underlie, at least in part, DM1 pathogenesis. It has been previously shown that disaggregating RNA foci repletes free MBNL1, rescues DM1 spliceopathy, and alleviates associated symptoms such as myotonia. Using an FDA-approved drug library, we have screened for a reduction of CUG foci in patient muscle cells and identified the HDAC inhibitor, vorinostat, as an inhibitor of foci formation; SERCA1 (sarcoplasmic\/endoplasmic reticulum Ca2+-ATPase) spliceopathy was also improved by vorinostat treatment. Vorinostat treatment in a mouse model of DM1 (human skeletal actin\u2013long repeat; HSALR) improved several spliceopathies, reduced muscle central nucleation, and restored chloride channel levels at the sarcolemma. Our in vitro and in vivo evidence showing amelioration of several DM1 disease markers marks vorinostat as a promising novel DM1 therapy.<\/jats:p>","DOI":"10.3390\/ijms24043794","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T03:09:32Z","timestamp":1676344172000},"page":"3794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Vorinostat Improves Myotonic Dystrophy Type 1 Splicing Abnormalities in DM1 Muscle Cell Lines and Skeletal Muscle from a DM1 Mouse Model"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6870-6013","authenticated-orcid":false,"given":"Nafisa","family":"Neault","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Eric Poulin Center for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6965-7372","authenticated-orcid":false,"given":"Aymeric","family":"Ravel-Chapuis","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Eric Poulin Center for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"School of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Baird","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Lunde","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Eric Poulin Center for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Poirier","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliyan","family":"Staykov","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5171-9408","authenticated-orcid":false,"given":"Julio","family":"Plaza-Diaz","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada"},{"name":"Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Medina","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0995-2572","authenticated-orcid":false,"given":"Francisco","family":"Abad\u00eda-Molina","sequence":"additional","affiliation":[{"name":"Institute of Nutrition and Food Technology \u201cJos\u00e9 Mataix\u201d, Biomedical Research Center, University of Granada, Armilla, 18016 Granada, Spain"},{"name":"Department of Cell Biology, School of Sciences, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard J.","family":"Jasmin","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Eric Poulin Center for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5867-6391","authenticated-orcid":false,"given":"Alex E.","family":"MacKenzie","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Eric Poulin Center for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/ejhg.2011.23","article-title":"Population frequency of myotonic dystrophy: Higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland","volume":"19","author":"Suominen","year":"2011","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1045","DOI":"10.1212\/WNL.0000000000011425","article-title":"Population-based prevalence of myotonic dystrophy type 1 using genetic analysis of statewide blood screening program","volume":"96","author":"Johnson","year":"2021","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1136\/bjo.77.9.579","article-title":"Cataract and myotonic dystrophy: The role of molecular diagnosis","volume":"77","author":"Reardon","year":"1993","journal-title":"Br. J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00415-009-0912-4","article-title":"Erectile dysfunction in myotonic dystrophy type 1 (DM1)","volume":"256","author":"Antonini","year":"2009","journal-title":"J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.5301\/ejo.5000565","article-title":"Primary cataract as a key to recognition of myotonic dystrophy type 1","volume":"25","author":"Voermans","year":"2015","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_6","first-page":"106","article-title":"Hypogonadism and erectile dysfunction in myotonic dystrophy type 1","volume":"32","author":"Peric","year":"2013","journal-title":"Acta Myol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/ng704","article-title":"Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy","volume":"29","author":"Savkur","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jns.2008.08.037","article-title":"A cross-sectional study for glucose intolerance of myotonic dystrophy","volume":"276","author":"Matsumura","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1212\/WNL.52.8.1658","article-title":"A 10-year study of mortality in a cohort of patients with myotonic dystrophy","volume":"52","author":"Mathieu","year":"1999","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1126\/science.1546325","article-title":"Myotonic dystrophy mutation: An unstable CTG repeat in the 3\u2032 untranslated region of the gene","volume":"255","author":"Mahadevan","year":"1992","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1042\/BST0371281","article-title":"Pathogenic mechanisms of myotonic dystrophy","volume":"37","author":"Lee","year":"2009","journal-title":"Biochem. Soc. Trans."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/0140-6736(92)90729-M","article-title":"Unstable DNA sequence in myotonic dystrophy","volume":"339","author":"Harley","year":"1992","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/0092-8674(92)90154-5","article-title":"Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3\u2032 end of a transcript encoding a protein kinase family member","volume":"68","author":"Brook","year":"1992","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/ng0692-192","article-title":"Correlation between CTG trinucleotide repeat length and frequency of severe congenital myotonic dystrophy","volume":"1","author":"Tsilfidis","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1093\/nar\/27.17.3534","article-title":"Visualization of double-stranded RNAs from the myotonic dystrophy protein kinase gene and interactions with CUG-binding protein","volume":"27","author":"Michalowski","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"31079","DOI":"10.1074\/jbc.272.49.31079","article-title":"CUG repeats present in myotonin kinase RNA form metastable \u201cslippery\u201d hairpins","volume":"272","author":"Napierala","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7388","DOI":"10.1073\/pnas.94.14.7388","article-title":"Expansion of a CUG trinucleotide repeat in the 3\u2032 untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts","volume":"94","author":"Davis","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","first-page":"760","article-title":"Ribonuclear inclusions in skeletal muscle in myotonic dystrophy types 1 and 2","volume":"54","author":"Mankodi","year":"2003","journal-title":"Ann. Neurol. Off. J. Am. Neurol. Assoc. Child Neurol. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4439","DOI":"10.1093\/emboj\/19.17.4439","article-title":"Recruitment of human muscleblind proteins to (CUG) n expansions associated with myotonic dystrophy","volume":"19","author":"Miller","year":"2000","journal-title":"EMBO J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/hmg\/ddh056","article-title":"Muscleblind protein, MBNL1\/EXP, binds specifically to CHHG repeats","volume":"13","author":"Kino","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1093\/hmg\/ddl132","article-title":"Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy","volume":"15","author":"Lin","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1126\/science.1088583","article-title":"A muscleblind knockout model for myotonic dystrophy","volume":"302","author":"Kanadia","year":"2003","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4645","DOI":"10.1093\/hmg\/dds306","article-title":"Mouse model of muscleblind-like 1 overexpression: Skeletal muscle effects and therapeutic promise","volume":"21","author":"Chamberlain","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1126\/science.1173110","article-title":"Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA","volume":"325","author":"Wheeler","year":"2009","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nature11362","article-title":"Targeting nuclear RNA for in vivo correction of myotonic dystrophy","volume":"488","author":"Wheeler","year":"2012","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/S1525-0016(03)00068-6","article-title":"Hammerhead ribozyme-mediated destruction of nuclear foci in myotonic dystrophy myoblasts","volume":"7","author":"Langlois","year":"2003","journal-title":"Mol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"De Serres-Berard, T., Ait Benichou, S., Jauvin, D., Boutjdir, M., Puymirat, J., and Chahine, M. (2022). Recent Progress and Challenges in the Development of Antisense Therapies for Myotonic Dystrophy Type 1. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113359"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1089\/hum.2022.069","article-title":"Enhanced Delivery of Ligand-Conjugated Antisense Oligonucleotides (C16-HA-ASO) Targeting Dystrophia Myotonica Protein Kinase Transcripts for the Treatment of Myotonic Dystrophy Type 1","volume":"33","author":"Jauvin","year":"2022","journal-title":"Hum. Gene. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41434-022-00316-7","article-title":"Antisense oligonucleotides as a potential treatment for brain deficits observed in myotonic dystrophy type 1","volume":"29","author":"Jauvin","year":"2022","journal-title":"Gene. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.yexcr.2016.02.013","article-title":"Reliable and versatile immortal muscle cell models from healthy and myotonic dystrophy type 1 primary human myoblasts","volume":"342","author":"Pantic","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1093\/hmg\/ddm239","article-title":"Molecular mechanisms responsible for aberrant splicing of SERCA1 in myotonic dystrophy type 1","volume":"16","author":"Hino","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1093\/hmg\/ddi223","article-title":"Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic\/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1","volume":"14","author":"Kimura","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/108705719900400206","article-title":"A simple statistical parameter for use in evaluation and validation of high throughput screening assays","volume":"4","author":"Zhang","year":"1999","journal-title":"J. Biomol. Screen."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1093\/hmg\/ddx190","article-title":"A flow cytometry-based screen identifies MBNL1 modulators that rescue splicing defects in myotonic dystrophy type I","volume":"26","author":"Zhang","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1093\/hmg\/ddy245","article-title":"Pharmacological and physiological activation of AMPK improves the spliceopathy in DM1 mouse muscles","volume":"27","author":"Jasmin","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e00155-19","DOI":"10.1128\/MCB.00155-19","article-title":"Correction of glycogen synthase kinase 3\u03b2 in myotonic dystrophy 1 reduces the mutant RNA and improves postnatal survival of DMSXL mice","volume":"39","author":"Wang","year":"2019","journal-title":"Mol. Cell. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature11556","article-title":"A call for transparent reporting to optimize the predictive value of preclinical research","volume":"490","author":"Landis","year":"2012","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S1097-2765(02)00572-5","article-title":"Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing","volume":"10","author":"Savkur","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_39","first-page":"3952","article-title":"Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy","volume":"117","author":"Wheeler","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"712583","DOI":"10.3389\/fphys.2021.712583","article-title":"Brief Report: Case Comparison of Therapy With the Histone Deacetylase Inhibitor Vorinostat in a Neonatal Calf Model of Pulmonary Hypertension","volume":"12","author":"Applegate","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/sj.bjc.6603463","article-title":"Cancer biology: Mechanism of antitumour action of vorinostat (suberoylanilide hydroxamic acid), a novel histone deacetylase inhibitor","volume":"95","author":"Richon","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1634\/theoncologist.12-10-1247","article-title":"FDA approval summary: Vorinostat for treatment of advanced primary cutaneous T-cell lymphoma","volume":"12","author":"Mann","year":"2007","journal-title":"Oncologist"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1158\/1535-7163.MCT-10-0572","article-title":"The histone deacetylase inhibitor, vorinostat, reduces tumor growth at the metastatic bone site and associated osteolysis, but promotes normal bone loss","volume":"9","author":"Pratap","year":"2010","journal-title":"Mol. Cancer Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1476-4598-9-49","article-title":"Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo","volume":"9","author":"Hrzenjak","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/carcin\/bgs319","article-title":"The combination of the histone deacetylase inhibitor vorinostat and synthetic triterpenoids reduces tumorigenesis in mouse models of cancer","volume":"34","author":"Tran","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1158\/1078-0432.CCR-07-0162","article-title":"Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies","volume":"13","author":"Ramalingam","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1007\/s10637-010-9447-x","article-title":"A phase I pharmacokinetic study of pulse-dose vorinostat with flavopiridol in solid tumors","volume":"29","author":"Dickson","year":"2011","journal-title":"Investig. New Drugs"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00280-013-2220-z","article-title":"Clinical pharmacology profile of vorinostat, a histone deacetylase inhibitor","volume":"72","author":"Iwamoto","year":"2013","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4395","DOI":"10.1074\/jbc.M116.770578","article-title":"Normalization of hepatic homeostasis in the Npc1nmf164 mouse model of Niemann-Pick type C disease treated with the histone deacetylase inhibitor vorinostat","volume":"292","author":"Munkacsi","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Debacker, K., Frizzell, A., Gleeson, O., Kirkham-McCarthy, L., Mertz, T., and Lahue, R.S. (2012). Histone deacetylase complexes promote trinucleotide repeat expansions. PLoS Biol., 10.","DOI":"10.1371\/journal.pbio.1001257"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejphar.2014.07.041","article-title":"Gemcitabine: Metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer","volume":"741","author":"Monteiro","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1093\/hmg\/ddt542","article-title":"High-content screening identifies small molecules that remove nuclear foci, affect MBNL distribution and CELF1 protein levels via a PKC-independent pathway in myotonic dystrophy cell lines","volume":"23","author":"Ketley","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1136\/jnnp-2014-309153","article-title":"Spinocerebellar ataxia type 36 exists in diverse populations and can be caused by a short hexanucleotide GGCCTG repeat expansion","volume":"86","author":"Obayashi","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.brainres.2018.12.045","article-title":"Suppression of the yeast elongation factor Spt4 ortholog reduces expanded SCA36 GGCCUG repeat aggregation and cytotoxicity","volume":"1711","author":"Furuta","year":"2019","journal-title":"Brain Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1093\/brain\/awy231","article-title":"Improved mobility with metformin in patients with myotonic dystrophy type 1: A randomized controlled trial","volume":"141","author":"Bassez","year":"2018","journal-title":"Brain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e262","DOI":"10.1038\/mtna.2015.35","article-title":"In vitro and in vivo modulation of alternative splicing by the biguanide metformin","volume":"4","author":"Laustriat","year":"2015","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Neault, N., O\u2019Reilly, S., Baig, A.T., Plaza-Diaz, J., Azimi, M., Farooq, F., Baird, S.D., and MacKenzie, A. (2021). High-throughput kinome-RNAi screen identifies protein kinase R activator (PACT) as a novel genetic modifier of CUG foci integrity in myotonic dystrophy type 1 (DM1). PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0256276"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1124\/jpet.115.226969","article-title":"Identification and characterization of modified antisense oligonucleotides targeting DMPK in mice and nonhuman primates for the treatment of myotonic dystrophy type 1","volume":"355","author":"Pandey","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1126\/science.289.5485.1769","article-title":"Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat","volume":"289","author":"Mankodi","year":"2000","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Bustin, S.A., Benes, V., Garson, J.A., Hellemans, J., Huggett, J., Kubista, M., Mueller, R., Nolan, T., Pfaffl, M.W., and Shipley, G.L. (2009). The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments, Oxford University Press.","DOI":"10.1373\/clinchem.2008.112797"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3794\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:34:39Z","timestamp":1760121279000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3794"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,14]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043794"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043794","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,14]]}}}