Nakamori, M & Takahashi, MP Myotonic dystrophy. In: Takeda S, Miyagoe-Suzuki Y, Mori-Yoshimura M, editors. Translational research in muscular dystrophy. Tokyo: Springer Japan; 2016. p. 39–61.
Johnson NE, Butterfield RJ, Mayne K, Newcomb T, Imburgia C, Dunn D, et al. Population Based Prevalence of Myotonic Dystrophy Type 1 Using Genetic Analysis of State-wide Blood Screening Program. Neurology. 2021;96:e1045–e1053.
Ibanez K, Jadhav B, Zanovello M, Gagliardi D, Clarkson C, Facchini S, et al. Increased frequency of repeat expansion mutations across different populations. Nat Med. 2024;30:3357–68.
Wenninger S, Montagnese F, Schoser B. Core Clinical Phenotypes in Myotonic Dystrophies. Front Neurol. 2018;9:303.
Wahbi K, Babuty D, Probst V, Wissocque L, Labombarda F, Porcher R, et al. Incidence and predictors of sudden death, major conduction defects and sustained ventricular tachyarrhythmias in 1388 patients with myotonic dystrophy type 1. Eur Heart J. 2017;38:751–58.
White M. Patient Input to Inform the Development of Central Nervous System Outcome Measures in Myotonic Dystrophy. Ther Innov Regul Sci. 2020;54:1010–17.
Peric S, Ivanovic V, Ashley EJ, Esparis B, Campbell C, Wenninger S, et al. International collaboration to improve knowledge on myotonic dystrophy type 2. J Neuromuscul Dis. 2024;11:1229–37.
Liao Q, Zhang Y, He J, Huang K. Global Prevalence of Myotonic Dystrophy: An Updated Systematic Review and Meta-Analysis. Neuroepidemiology. 2022;56:163–73.
Wenninger S, Cumming SA, Gutschmidt K, Okkersen K, Jimenez-Moreno AC, Daidj F, et al. Associations Between Variant Repeat Interruptions and Clinical Outcomes in Myotonic Dystrophy Type 1. Neurol Genet. 2021;7:e572.
Lopez Castel A, Nakamori M, Tome S, Chitayat D, Gourdon G, Thornton CA, et al. Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues. Hum Mol Genet. 2011;20:1–15.
Nakamori M, Hamanaka K, Thomas JD, Wang ET, Hayashi YK, Takahashi MP, et al. Aberrant Myokine Signaling in Congenital Myotonic Dystrophy. Cell Rep. 2017;21:1240–52.
Ashizawa T, Anvret M, Baiget M, Barcelo JM, Brunner H, Cobo AM, et al. Characteristics of intergenerational contractions of the CTG repeat in myotonic dystrophy. Am J Hum Genet. 1994;54:414–23.
Lagrue E, Dogan C, De Antonio M, Audic F, Bach N, Barnerias C, et al. A large multicenter study of pediatric myotonic dystrophy type 1 for evidence-based management. Neurology. 2019;92:e852–e65.
Nakamori M, Sobczak K, Moxley RT 3rd, Thornton CA. Scaled-down genetic analysis of myotonic dystrophy type 1 and type 2. Neuromuscul Disord. 2009;19:759–62.
Nakamori M, Shimizu H, Ogawa K, Hasuike Y, Nakajima T, Sakurai H, et al. Cell type-specific abnormalities of central nervous system in myotonic dystrophy type 1. Brain Commun. 2022;4:fcac154.
Schmidt MHM, Pearson CE. Disease-associated repeat instability and mismatch repair. DNA Repair (Amst). 2016;38:117–26.
Nakamori M, Gourdon G, Thornton CA. Stabilization of expanded (CTG)*(CAG) repeats by antisense oligonucleotides. Mol Ther. 2011;19:2222–7.
Lee KY, Li M, Manchanda M, Batra R, Charizanis K, Mohan A, et al. Compound loss of muscleblind-like function in myotonic dystrophy. EMBO Mol Med. 2013;5:1887–900.
Koshelev M, Sarma S, Price RE, Wehrens XH, Cooper TA. Heart-specific overexpression of CUGBP1 reproduces functional and molecular abnormalities of myotonic dystrophy type 1. Hum Mol Genet. 2010;19:1066–75.
Mankodi A, Takahashi MP, Jiang H, Beck CL, Bowers WJ, Moxley RT, et al. Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol Cell. 2002;10:35–44.
Savkur RS, Philips AV, Cooper TA. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet. 2001;29:40–7.
Freyermuth F, Rau F, Kokunai Y, Linke T, Sellier C, Nakamori M, et al. Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy. Nat Commun. 2016;7:11067.
Kimura T, Nakamori M, Lueck JD, Pouliquin P, Aoike F, Fujimura H, et al. Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1. Hum Mol Genet. 2005;14:2189–200.
Tang ZZ, Yarotskyy V, Wei L, Sobczak K, Nakamori M, Eichinger K, et al. Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of Ca(V)1.1 calcium channel. Hum Mol Genet. 2012;21:1312–24.
Fugier C, Klein AF, Hammer C, Vassilopoulos S, Ivarsson Y, Toussaint A, et al. Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. Nat Med. 2011;17:720–5.
Nakamori M, Kimura T, Fujimura H, Takahashi MP, Sakoda S. Altered mRNA splicing of dystrophin in type 1 myotonic dystrophy. Muscle Nerve. 2007;36:251–7.
Nakamori M, Kimura T, Kubota T, Matsumura T, Sumi H, Fujimura H, et al. Aberrantly spliced alpha-dystrobrevin alters alpha-syntrophin binding in myotonic dystrophy type 1. Neurology. 2008;70:677–85.
Nakamori M, Sobczak K, Puwanant A, Welle S, Eichinger K, Pandya S, et al. Splicing biomarkers of disease severity in myotonic dystrophy. Ann Neurol. 2013;74:862–72.
Provenzano M, Ikegami K, Bates K, Gaynor A, Hartman JM, Jones A, et al. The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1. J Clin Invest. 2025;135:e185426.
Sergeant N, Sablonniere B, Schraen-Maschke S, Ghestem A, Maurage CA, Wattez A, et al. Dysregulation of human brain microtubule-associated tau mRNA maturation in myotonic dystrophy type 1. Hum Mol Genet. 2001;10:2143–55.
Jiang H, Mankodi A, Swanson MS, Moxley RT, Thornton CA. Myotonic dystrophy type 1 is associated with nuclear foci of mutant RNA, sequestration of muscleblind proteins and deregulated alternative splicing in neurons. Hum Mol Genet. 2004;13:3079–88.
Suenaga K, Lee KY, Nakamori M, Tatsumi Y, Takahashi MP, Fujimura H, et al. Muscleblind-like 1 knockout mice reveal novel splicing defects in the myotonic dystrophy brain. PLoS One. 2012;7:e33218.
Furuta M, Kimura T, Nakamori M, Matsumura T, Fujimura H, Jinnai K, et al. Macroscopic and microscopic diversity of missplicing in the central nervous system of patients with myotonic dystrophy type 1. Neuroreport. 2018;29:235–40.
Sznajder LJ, Khan M, Ciesiolka A, Tadross M, Nutter CA, Taylor K, et al. Autism-related traits in myotonic dystrophy type 1 model mice are due to MBNL sequestration and RNA mis-splicing of autism-risk genes. Nat Neurosci. 2025. https://doi.org/10.1038/s41593-025-01943-0.
Auxerre-Plantie E, Nakamori M, Renaud Y, Huguet A, Choquet C, Dondi C, et al. Straightjacket/alpha2delta3 deregulation is associated with cardiac conduction defects in myotonic dystrophy type 1. Elife. 2019;8:e51114.
Rau F, Freyermuth F, Fugier C, Villemin JP, Fischer MC, Jost B, et al. Misregulation of miR-1 processing is associated with heart defects in myotonic dystrophy. Nat Struct Mol Biol. 2011;18:840–5.
Souidi A, Nakamori M, Zmojdzian M, Jagla T, Renaud Y, Jagla K. Deregulations of miR-1 and its target Multiplexin promote dilated cardiomyopathy associated with myotonic dystrophy type 1. EMBO Rep. 2023;24. e56616.
Wang ET, Cody NA, Jog S, Biancolella M, Wang TT, Treacy DJ, et al. Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. Cell. 2012;150:710–24.
Batra R, Charizanis K, Manchanda M, Mohan A, Li M, Finn DJ, et al. Loss of MBNL leads to disruption of developmentally regulated alternative polyadenylation in RNA-mediated disease. Mol Cell. 2014;56:311–22.
Vlasova IA, Tahoe NM, Fan D, Larsson O, Rattenbacher B, Sternjohn JR, et al. Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1. Mol Cell. 2008;29:263–70.
Huichalaf C, Sakai K, Jin B, Jones K, Wang GL, Schoser B, et al. Expansion of CUG RNA repeats causes stress and inhibition of translation in myotonic dystrophy 1 (DM1) cells. FASEB J. 2010;24:3706–19.
Sellier C, Cerro-Herreros E, Blatter M, Freyermuth F, Gaucherot A, Ruffenach F, et al. rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences. Nat Commun. 2018;9:2009.
Misra C, Bangru S, Lin F, Lam K, Koenig SN, Lubbers ER, et al. Aberrant Expression of a Non-muscle RBFOX2 Isoform Triggers Cardiac Conduction Defects in Myotonic Dystrophy. Dev Cell. 2020;52:748–63.e6.
Crawford Parks TE, Marcellus KA, Peladeau C, Jasmin BJ, Ravel-Chapuis A. Overexpression of Staufen1 in DM1 mouse skeletal muscle exacerbates dystrophic and atrophic features. Hum Mol Genet. 2020;29:2185–99.
Zu T, Gibbens B, Doty NS, Gomes-Pereira M, Huguet A, Stone MD, et al. Non-ATG-initiated translation directed by microsatellite expansions. Proc Natl Acad Sci USA. 2011;108:260–5.
Guo S, Nguyen L, Ranum LPW. RAN proteins in neurodegenerative disease: Repeating themes and unifying therapeutic strategies. Curr Opin Neurobiol. 2022;72:160–70.
Zu T, Cleary JD, Liu Y, Banez-Coronel M, Bubenik JL, Ayhan F, et al. RAN Translation Regulated by Muscleblind Proteins in Myotonic Dystrophy Type 2. Neuron. 2017;95:1292–305.e5.
Kuyumcu-Martinez NM, Wang GS, Cooper TA. Increased steady-state levels of CUGBP1 in myotonic dystrophy 1 are due to PKC-mediated hyperphosphorylation. Mol Cell. 2007;28:68–78.
Jones K, Wei C, Iakova P, Bugiardini E, Schneider-Gold C, Meola G, et al. GSK3beta mediates muscle pathology in myotonic dystrophy. J Clin Invest. 2012;122:4461–72.
Salisbury E, Sakai K, Schoser B, Huichalaf C, Schneider-Gold C, Nguyen H, et al. Ectopic expression of cyclin D3 corrects differentiation of DM1 myoblasts through activation of RNA CUG-binding protein, CUGBP1. Exp Cell Res. 2008;314:2266–78.
Brockhoff M, Rion N, Chojnowska K, Wiktorowicz T, Eickhorst C, Erne B, et al. Targeting deregulated AMPK/mTORC1 pathways improves muscle function in myotonic dystrophy type I. J Clin Invest. 2017;127:549–63.
Hasuike Y, Mochizuki H, Nakamori M. Cellular Senescence and Aging in Myotonic Dystrophy. Int J Mol Sci. 2022;23:2339.
Furling D, Coiffier L, Mouly V, Barbet JP, St Guily JL, Taneja K, et al. Defective satellite cells in congenital myotonic dystrophy. Hum Mol Genet. 2001;10:2079–87.
Bigot A, Klein AF, Gasnier E, Jacquemin V, Ravassard P, Butler-Browne G, et al. Large CTG repeats trigger p16-dependent premature senescence in myotonic dystrophy type 1 muscle precursor cells. Am J Pathol. 2009;174:1435–42.
Toscano A, Messina S, Campo GM, Di Leo R, Musumeci O, Rodolico C, et al. Oxidative stress in myotonic dystrophy type 1. Free Radic Res. 2005;39:771–6.
Garcia-Puga M, Saenz-Antonanzas A, Fernandez-Torron R, Munain AL, Matheu A. Myotonic Dystrophy type 1 cells display impaired metabolism and mitochondrial dysfunction that are reversed by metformin. Aging (Albany NY). 2020;12:6260–75.
Hasuike Y, Mochizuki H, Nakamori M. Expanded CUG Repeat RNA Induces Premature Senescence in Myotonic Dystrophy Model Cells. Front Genet. 2022;13:865811.
Garcia-Puga M, Saenz-Antonanzas A, Gerenu G, Arrieta A, Fernandez-Torron R, Zulaica M, et al. Senescence plays a role in Myotonic Dystrophy type 1. JCI Insight. 2022;7:e159357.
Mulders SA, van den Broek WJ, Wheeler TM, Croes HJ, van Kuik-Romeijn P, de Kimpe SJ, et al. Triplet-repeat oligonucleotide-mediated reversal of RNA toxicity in myotonic dystrophy. Proc Natl Acad Sci USA. 2009;106:13915–20.
Wheeler TM, Leger AJ, Pandey SK, MacLeod AR, Nakamori M, Cheng SH, et al. Targeting nuclear RNA for in vivo correction of myotonic dystrophy. Nature. 2012;488:111–5.
Pandey SK, Wheeler TM, Justice SL, Kim A, Younis HS, Gattis D, et al. Identification and characterization of modified antisense oligonucleotides targeting DMPK in mice and nonhuman primates for the treatment of myotonic dystrophy type 1. J Pharm Exp Ther. 2015;355:329–40.
Wojtkowiak-Szlachcic A, Taylor K, Stepniak-Konieczna E, Sznajder LJ, Mykowska A, Sroka J, et al. Short antisense-locked nucleic acids (all-LNAs) correct alternative splicing abnormalities in myotonic dystrophy. Nucleic Acids Res. 2015;43:3318–31.
Klein AF, Varela MA, Arandel L, Holland A, Naouar N, Arzumanov A, et al. Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice. J Clin Invest. 2019;129:4739–44.
Thornton CA, Moxley RT 3rd, Eichinger K, Heatwole C, Mignon L, Arnold WD, et al. Antisense oligonucleotide targeting DMPK in patients with myotonic dystrophy type 1: a multicentre, randomised, dose-escalation, placebo-controlled, phase 1/2a trial. Lancet Neurol. 2023;22:218–28.
Weeden T, Picariello T, Quinn B, Spring S, Shen PY, Qiu Q, et al. FORCE platform overcomes barriers of oligonucleotide delivery to muscle and corrects myotonic dystrophy features in preclinical models. Commun Med (Lond). 2025;5:22.
Childs-Disney JL, Parkesh R, Nakamori M, Thornton CA, Disney MD. Rational design of bioactive, modularly assembled aminoglycosides targeting the RNA that causes myotonic dystrophy type 1. ACS Chem Biol. 2012;7:1984–93.
Parkesh R, Childs-Disney JL, Nakamori M, Kumar A, Wang E, Wang T, et al. Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching. J Am Chem Soc. 2012;134:4731–42.
Ofori LO, Hoskins J, Nakamori M, Thornton CA, Miller BL. From dynamic combinatorial ‘hit’ to lead: in vitro and in vivo activity of compounds targeting the pathogenic RNAs that cause myotonic dystrophy. Nucleic Acids Res. 2012;40:6380–90.
Li J, Nakamori M, Matsumoto J, Murata A, Dohno C, Kiliszek A, et al. A Dimeric 2,9-Diamino-1,10-phenanthroline Derivative Improves Alternative Splicing in Myotonic Dystrophy Type 1 Cell and Mouse Models. Chemistry. 2018;24:18115–22.
Chen G, Masuda A, Konishi H, Ohkawara B, Ito M, Kinoshita M, et al. Phenylbutazone induces expression of MBNL1 and suppresses formation of MBNL1-CUG RNA foci in a mouse model of myotonic dystrophy. Sci Rep. 2016;6:25317.
Matsumoto J, Nakamori M, Okamoto T, Murata A, Dohno C, Nakatani K. The Dimeric Form of 1,3-Diaminoisoquinoline Derivative Rescued the Mis-splicing of Atp2a1 and Clcn1 Genes in Myotonic Dystrophy Type 1 Mouse Model. Chemistry. 2020;26:14305–09.
Herrendorff R, Faleschini MT, Stiefvater A, Erne B, Wiktorowicz T, Kern F, et al. Identification of Plant-derived Alkaloids with Therapeutic Potential for Myotonic Dystrophy Type I. J Biol Chem. 2016;291:17165–77.
Warf MB, Nakamori M, Matthys CM, Thornton CA, Berglund JA. Pentamidine reverses the splicing defects associated with myotonic dystrophy. Proc Natl Acad Sci USA. 2009;106:18551–6.
Coonrod LA, Nakamori M, Wang W, Carrell S, Hilton CL, Bodner MJ, et al. Reducing levels of toxic RNA with small molecules. ACS Chem Biol. 2013;8:2528–37.
Siboni RB, Bodner MJ, Khalifa MM, Docter AG, Choi JY, Nakamori M, et al. Biological Efficacy and Toxicity of Diamidines in Myotonic Dystrophy Type 1 Models. J Med Chem. 2015;58:5770–80.
Siboni RB, Nakamori M, Wagner SD, Struck AJ, Coonrod LA, Harriott SA, et al. Actinomycin D Specifically Reduces Expanded CUG Repeat RNA in Myotonic Dystrophy Models. Cell Rep. 2015;13:2386–94.
Reddy K, Jenquin JR, McConnell OL, Cleary JD, Richardson JI, Pinto BS, et al. A CTG repeat-selective chemical screen identifies microtubule inhibitors as selective modulators of toxic CUG RNA levels. Proc Natl Acad Sci USA. 2019;116:20991–1000.
Wang M, Weng WC, Stock L, Lindquist D, Martinez A, Gourdon G, et al. Correction of Glycogen Synthase Kinase 3beta in Myotonic Dystrophy 1 Reduces the Mutant RNA and Improves Postnatal Survival of DMSXL Mice. Mol Cell Biol. 2019;39:e00155-19.
Cisco LA, Sipple MT, Edwards KM, Thornton CA, Lueck JD. Verapamil mitigates chloride and calcium bi-channelopathy in a myotonic dystrophy mouse model. J Clin Invest. 2024;134:e173576.
Heatwole C, Luebbe E, Rosero S, Eichinger K, Martens W, Hilbert J, et al. Mexiletine in Myotonic Dystrophy Type 1: A Randomized, Double-Blind, Placebo-Controlled Trial. Neurology. 2021;96:e228–e40.
Bassez G, Audureau E, Hogrel JY, Arrouasse R, Baghdoyan S, Bhugaloo H, et al. Improved mobility with metformin in patients with myotonic dystrophy type 1: a randomized controlled trial. Brain. 2018;141:2855–65.
Horrigan J, Gomes TB, Snape M, Nikolenko N, McMorn A, Evans S, et al. A Phase 2 Study of AMO-02 (Tideglusib) in Congenital and Childhood-Onset Myotonic Dystrophy Type 1 (DM1). Pediatr Neurol. 2020;112:84–93.
Nakamori M, Nakatani D, Sato T, Hasuike Y, Kon S, Saito T, et al. Erythromycin for myotonic dystrophy type 1: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. EClinicalMedicine. 2024;67:102390.
Arandel L, Matloka M, Klein AF, Rau F, Sureau A, Ney M, et al. Reversal of RNA toxicity in myotonic dystrophy via a decoy RNA-binding protein with high affinity for expanded CUG repeats. Nat Biomed Eng. 2022;6:207–20.
Imai T, Miyai M, Nemoto J, Tamai T, Ohta M, Yagi Y, et al. Pentatricopeptide repeat protein targeting CUG repeat RNA ameliorates RNA toxicity in a myotonic dystrophy type 1 mouse model. Sci Transl Med. 2025;17:eadq2005.
Kanadia RN, Shin J, Yuan Y, Beattie SG, Wheeler TM, Thornton CA, et al. Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy. Proc Natl Acad Sci USA. 2006;103:11748–53.
Hu RC, Zhang Y, Nitschke L, Johnson SJ, Hurley AE, Lagor WR, et al. MBNL overexpression rescues cardiac phenotypes in a myotonic dystrophy type 1 heart mouse model. J Clin Invest. 2025;135:e186416.
Cerro-Herreros E, Sabater-Arcis M, Fernandez-Costa JM, Moreno N, Perez-Alonso M, Llamusi B, et al. miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models. Nat Commun. 2018;9:2482.
Gonzalez-Martinez I, Cerro-Herreros E, Moreno N, Garcia-Rey A, Espinosa-Espinosa J, Carrascosa-Saez M, et al. Peptide-conjugated antimiRs improve myotonic dystrophy type 1 phenotypes by promoting endogenous MBNL1 expression. Mol Ther Nucleic Acids. 2023;34:102024.
Lo Scrudato M, Poulard K, Sourd C, Tome S, Klein AF, Corre G, et al. Genome Editing of Expanded CTG Repeats within the Human DMPK Gene Reduces Nuclear RNA Foci in the Muscle of DM1 Mice. Mol Ther. 2019;27:1372–88.
Cardinali B, Provenzano C, Izzo M, Voellenkle C, Battistini J, Strimpakos G, et al. Time-controlled and muscle-specific CRISPR/Cas9-mediated deletion of CTG-repeat expansion in the DMPK gene. Mol Ther Nucleic Acids. 2022;27:184–99.
Pinto BS, Saxena T, Oliveira R, Mendez-Gomez HR, Cleary JD, Denes LT, et al. Impeding Transcription of Expanded Microsatellite Repeats by Deactivated Cas9. Mol Cell. 2017;68:479–90 e5.
Batra R, Nelles DA, Roth DM, Krach F, Nutter CA, Tadokoro T, et al. The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy type 1. Nat Biomed Eng. 2021;5:157–68.
Nakamori M, Panigrahi GB, Lanni S, Gall-Duncan T, Hayakawa H, Tanaka H, et al. A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo. Nat Genet. 2020;52:146–59.
Hasuike Y, Tanaka H, Gall-Duncan T, Mehkary M, Nakatani K, Pearson CE, et al. CAG repeat-binding small molecule improves motor coordination impairment in a mouse model of Dentatorubral-pallidoluysian atrophy. Neurobiol Dis. 2022;163:105604.