{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:12:29Z","timestamp":1790716349381,"version":"4.1.0"},"reference-count":142,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["1R01AR079884"],"award-info":[{"award-number":["1R01AR079884"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Facioscapulohumeral muscular dystrophy (FSHD) is arguably one of the most challenging genetic diseases to understand and treat. The disease is caused by epigenetic dysregulation of a macrosatellite repeat, either by contraction of the repeat or by mutations in silencing proteins. Both cases lead to chromatin relaxation and, in the context of a permissive allele, pathogenic misexpression of DUX4 in skeletal muscle. The complex nature of the locus and the fact that FSHD is a toxic, gain-of-function disease present unique challenges for the design of therapeutic strategies. There are three major DUX4-targeting avenues of therapy for FSHD: small molecules, oligonucleotide therapeutics, and CRISPR-based approaches. Here, we evaluate the preclinical progress of each avenue, and discuss efforts being made to overcome major hurdles to translation.<\/jats:p>","DOI":"10.3390\/jpm12060865","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T08:41:33Z","timestamp":1653468093000},"page":"865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["FSHD Therapeutic Strategies: What Will It Take to Get to Clinic?"],"prefix":"10.3390","volume":"12","author":[{"given":"Charis L.","family":"Himeda","sequence":"first","affiliation":[{"name":"The Department of Pharmacology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Jones","sequence":"additional","affiliation":[{"name":"The Department of Pharmacology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref_1","unstructured":"Padberg, G.W. (1982). Facioscapulohumeral Disease. [Ph.D. Thesis, Leiden University]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1212\/WNL.0000000000000797","article-title":"Population-based incidence and prevalence of facioscapulohumeral dystrophy","volume":"83","author":"Deenen","year":"2014","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s11910-016-0667-0","article-title":"Facioscapulohumeral Dystrophy","volume":"16","author":"Wang","year":"2016","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_4","unstructured":"Orphanet (2022, May 23). Prevalence and Incidence of Rare Diseases: Bibliographic Data. Orphanet Report Series: Rare Diseases Collection. Available online: http:\/\/www.orpha.net\/orphacom\/cahiers\/docs\/GB\/Prevalence_of_rare_diseases_by_alphabetical_list.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mus.20522","article-title":"Facioscapulohumeral muscular dystrophy","volume":"34","author":"Tawil","year":"2006","journal-title":"Muscle Nerve"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1007\/s00415-021-10591-w","article-title":"The socioeconomic burden of facioscapulohumeral muscular dystrophy","volume":"268","author":"Blokhuis","year":"2021","journal-title":"J. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1146\/annurev-genom-083118-014933","article-title":"The Genetics and Epigenetics of Facioscapulohumeral Muscular Dystrophy","volume":"20","author":"Himeda","year":"2019","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/ng.3858","article-title":"DUX-family transcription factors regulate zygotic genome activation in placental mammals","volume":"49","author":"Planet","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/ng.3844","article-title":"Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL\/HERVL retrotransposons","volume":"49","author":"Hendrickson","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/ng.3846","article-title":"Conservation and innovation in the DUX4-family gene network","volume":"49","author":"Whiddon","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"859930","DOI":"10.3389\/fmed.2022.859930","article-title":"Therapeutic Strategies for Dystrophin Replacement in Duchenne Muscular Dystrophy","volume":"9","author":"Mbakam","year":"2022","journal-title":"Front. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.2217\/nmt-2020-0066","article-title":"Unmet needs and evolving treatment for limb girdle muscular dystrophies","volume":"11","author":"Pozsgai","year":"2021","journal-title":"Neurodegener. Dis. Manag."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Soltanzadeh, P. (2022). Myotonic Dystrophies: A Genetic Overview. Genes, 13.","DOI":"10.3390\/genes13020367"},{"key":"ref_14","first-page":"1640","article-title":"Congenital Muscular Dystrophy and Congenital Myopathy","volume":"25","author":"Butterfield","year":"2019","journal-title":"Continuum"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/mus.26782","article-title":"Emery-Dreifuss muscular dystrophy","volume":"61","author":"Heller","year":"2020","journal-title":"Muscle Nerve"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1006\/geno.1995.1166","article-title":"The FSHD-associated repeat, D4Z4, is a member of a dispersed family of homeobox-containing repeats, subsets of which are clustered on the short arms of the acrocentric chromosomes","volume":"28","author":"Lyle","year":"1995","journal-title":"Genomics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0378-1119(99)00267-X","article-title":"Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element","volume":"236","author":"Gabriels","year":"1999","journal-title":"Gene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1002\/ana.10057","article-title":"Complete allele information in the diagnosis of facioscapulohumeral muscular dystrophy by triple DNA analysis","volume":"50","author":"Lemmers","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/ng999","article-title":"Facioscapulohumeral muscular dystrophy is uniquely associated with one of the two variants of the 4q subtelomere","volume":"32","author":"Lemmers","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1126\/science.1189044","article-title":"A unifying genetic model for facioscapulohumeral muscular dystrophy","volume":"329","author":"Lemmers","year":"2010","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Snider, L., Geng, L.N., Lemmers, R.J., Kyba, M., Ware, C.B., Nelson, A.M., Tawil, R., Filippova, G.N., van der Maarel, S.M., and Tapscott, S.J. (2010). Facioscapulohumeral dystrophy: Incomplete suppression of a retrotransposed gene. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001181"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.1093\/hmg\/dds284","article-title":"Facioscapulohumeral muscular dystrophy family studies of DUX4 expression: Evidence for disease modifiers and a quantitative model of pathogenesis","volume":"21","author":"Jones","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1128\/MCB.00149-14","article-title":"Myogenic enhancers regulate expression of the facioscapulohumeral muscular dystrophy associated DUX4 gene","volume":"34","author":"Himeda","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1093\/hmg\/ddv315","article-title":"Endogenous DUX4 expression in FSHD myotubes is sufficient to cause cell death and disrupts RNA splicing and cell migration pathways","volume":"24","author":"Rickard","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1086\/519311","article-title":"Evolutionary conservation of a coding function for D4Z4, the tandem DNA repeat mutated in facioscapulohumeral muscular dystrophy","volume":"81","author":"Clapp","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00412-012-0380-y","article-title":"Evolution of DUX gene macrosatellites in placental mammals","volume":"121","author":"Leidenroth","year":"2012","journal-title":"Chromosoma"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Leidenroth, A., and Hewitt, J.E. (2010). A family history of DUX4: Phylogenetic analysis of DUXA, B, C and Duxbl reveals the ancestral DUX gene. BMC Evol. Biol., 10.","DOI":"10.1186\/1471-2148-10-364"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.molmed.2015.02.011","article-title":"Emerging preclinical animal models for FSHD","volume":"21","author":"Lek","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1212\/WNL.54.9.1848","article-title":"Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study","volume":"54","author":"Walter","year":"2000","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1212\/WNL.57.8.1434","article-title":"Randomized, double-blind, placebo-controlled trial of albuterol in facioscapulohumeral dystrophy","volume":"57","author":"Kissel","year":"2001","journal-title":"Neurology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.nmd.2006.08.005","article-title":"No effect of folic acid and methionine supplementation on D4Z4 methylation in patients with facioscapulohumeral muscular dystrophy","volume":"16","author":"Wohlgemuth","year":"2006","journal-title":"Neuromuscul. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s00415-006-0432-4","article-title":"Effects of training and albuterol on pain and fatigue in facioscapulohumeral muscular dystrophy","volume":"254","author":"Kalkman","year":"2007","journal-title":"J. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/ana.21338","article-title":"A phase I\/IItrial of MYO-029 in adult subjects with muscular dystrophy","volume":"63","author":"Wagner","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1002\/mus.26113","article-title":"Locally acting ACE-083 increases muscle volume in healthy volunteers","volume":"57","author":"Glasser","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.freeradbiomed.2014.09.014","article-title":"Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: A double-blind randomized controlled clinical trial","volume":"81","author":"Passerieux","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Statland, J.M., Campbell, C., Desai, U., Karam, C., Diaz-Manera, J., Guptill, J.T., Korngut, L., Genge, A., Tawil, R.N., and Elman, L. (Muscle Nerve, 2022). Randomized Phase 2 Study of ACE-083, a Muscle-Promoting Agent, in Facioscapulohumeral Muscular Dystrophy, Muscle Nerve, in press.","DOI":"10.1002\/mus.27558"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4658","DOI":"10.1111\/bcp.14884","article-title":"Phase 1 clinical trial of losmapimod in facioscapulohumeral dystrophy: Safety, tolerability, pharmacokinetics, and target engagement","volume":"87","author":"Mellion","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.drudis.2021.03.024","article-title":"Myotonic dystrophy type 1 drug development: A pipeline toward the market","volume":"26","author":"Artero","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Le Gall, L., Sidlauskaite, E., Mariot, V., and Dumonceaux, J. (2020). Therapeutic Strategies Targeting DUX4 in FSHD. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092886"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3233\/JND-200554","article-title":"Current Therapeutic Approaches in FSHD","volume":"8","author":"Wang","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.molmed.2020.09.008","article-title":"Therapeutic Approaches in Facioscapulohumeral Muscular Dystrophy","volume":"27","author":"Cohen","year":"2021","journal-title":"Trends Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13395-017-0134-x","article-title":"BET bromodomain inhibitors and agonists of the beta-2 adrenergic receptor identified in screens for compounds that inhibit DUX4 expression in FSHD muscle cells","volume":"7","author":"Campbell","year":"2017","journal-title":"Skelet. Muscle"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11837","DOI":"10.1074\/jbc.RA118.002633","article-title":"Protein kinase A activation inhibits DUX4 gene expression in myotubes from patients with facioscapulohumeral muscular dystrophy","volume":"293","author":"Cruz","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1124\/jpet.119.264689","article-title":"P38 alpha Regulates Expression of DUX4 in a Model of Facioscapulohumeral Muscular Dystrophy","volume":"374","author":"Rojas","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1124\/jpet.119.259663","article-title":"Clinically Advanced p38 Inhibitors Suppress DUX4 Expression in Cellular and Animal Models of Facioscapulohumeral Muscular Dystrophy","volume":"370","author":"Oliva","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.1093\/hmg\/ddt314","article-title":"Wnt\/beta-catenin signaling suppresses DUX4 expression and prevents apoptosis of FSHD muscle cells","volume":"22","author":"Block","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.ymthe.2018.04.019","article-title":"Identification of Epigenetic Regulators of DUX4-fl for Targeted Therapy of Facioscapulohumeral Muscular Dystrophy","volume":"26","author":"Himeda","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e31023","DOI":"10.7554\/eLife.31023","article-title":"NuRD and CAF-1-mediated silencing of the D4Z4 array is modulated by DUX4-induced MBD3L proteins","volume":"7","author":"Campbell","year":"2018","journal-title":"eLife"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4172\/2157-7412.1000303","article-title":"PARP1 Differentially Interacts with Promoter region of DUX4 Gene in FSHD Myoblasts","volume":"7","author":"Sharma","year":"2016","journal-title":"J. Genet. Syndr. Gene Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1080\/15592294.2015.1113798","article-title":"Increased DUX4 expression during muscle differentiation correlates with decreased SMCHD1 protein levels at D4Z4","volume":"10","author":"Balog","year":"2015","journal-title":"Epigenetics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eaay0271","DOI":"10.1126\/scitranslmed.aay0271","article-title":"Applying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy","volume":"12","author":"Lek","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1177\/1087057116651868","article-title":"Transcriptional Inhibitors Identified in a 160,000-Compound Small-Molecule DUX4 Viability Screen","volume":"21","author":"Choi","year":"2016","journal-title":"J. Biomol. Screen."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2044-5040-4-4","article-title":"High-throughput screening identifies inhibitors of DUX4-induced myoblast toxicity","volume":"4","author":"Bosnakovski","year":"2014","journal-title":"Skelet. Muscle"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eaaw7781","DOI":"10.1126\/sciadv.aaw7781","article-title":"A novel P300 inhibitor reverses DUX4-mediated global histone H3 hyperacetylation, target gene expression, and cell death","volume":"5","author":"Bosnakovski","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100075","DOI":"10.1016\/j.medidd.2020.100075","article-title":"Biologics vs. small molecules: Drug costs and patient access","volume":"9","author":"Makurvet","year":"2021","journal-title":"Med. Drug Discov."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.mce.2006.03.017","article-title":"The p38 MAPK signaling pathway: A major regulator of skeletal muscle development","volume":"252","author":"Keren","year":"2006","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5452","DOI":"10.1093\/hmg\/ddu270","article-title":"P38alpha MAPK underlies muscular dystrophy and myofiber death through a Bax-dependent mechanism","volume":"23","author":"Wissing","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fcell.2016.00091","article-title":"Regulation of Muscle Stem Cell Functions: A Focus on the p38 MAPK Signaling Pathway","volume":"4","author":"Segales","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.tips.2014.09.007","article-title":"Advances in kinase targeting: Current clinical use and clinical trials","volume":"35","author":"Zhang","year":"2014","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Vanderplanck, C., Ansseau, E., Charron, S., Stricwant, N., Tassin, A., Laoudj-Chenivesse, D., Wilton, S.D., Coppee, F., and Belayew, A. (2011). The FSHD Atrophic Myotube Phenotype Is Caused by DUX4 Expression. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026820"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ansseau, E., Vanderplanck, C., Wauters, A., Harper, S.Q., Coppee, F., and Belayew, A. (2017). Antisense Oligonucleotides Used to Target the DUX4 mRNA as Therapeutic Approaches in FaciosScapuloHumeral Muscular Dystrophy (FSHD). Genes, 8.","DOI":"10.3390\/genes8030093"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4817","DOI":"10.1093\/hmg\/ddv206","article-title":"DICER\/AGO-dependent epigenetic silencing of D4Z4 repeats enhanced by exogenous siRNA suggests mechanisms and therapies for FSHD","volume":"24","author":"Lim","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1093\/hmg\/ddw015","article-title":"Antisense targeting of 3\u2032 end elements involved in DUX4 mRNA processing is an efficient therapeutic strategy for facioscapulohumeral dystrophy: A new gene-silencing approach","volume":"25","author":"Marsollier","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1038\/mt.2016.111","article-title":"Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics","volume":"24","author":"Chen","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"16509","DOI":"10.1073\/pnas.1909649117","article-title":"Inhibition of DUX4 expression with antisense LNA gapmers as a therapy for facioscapulohumeral muscular dystrophy","volume":"117","author":"Lim","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.ymthe.2020.10.010","article-title":"DUX4 Transcript Knockdown with Antisense 2\u2032-O-Methoxyethyl Gapmers for the Treatment of Facioscapulohumeral Muscular Dystrophy","volume":"29","author":"Lim","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Lu-Nguyen, N., Malerba, A., Pineda, M.A., Dickson, G., and Popplewell, L.J. (Hum. Gene Ther., 2022). Improving molecular and histopathology in diaphragm muscle of the double transgenic ACTA1-MCM\/FLExDUX4 mouse model of FSHD with systemic antisense therapy, Hum. Gene Ther., ahead of print.","DOI":"10.1089\/hum.2021.251"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1093\/hmg\/ddab136","article-title":"Systemic antisense therapeutics inhibiting DUX4 expression ameliorates FSHD-like pathology in an FSHD mouse model","volume":"30","author":"Malerba","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1038\/mt.2012.68","article-title":"RNA interference inhibits DUX4-induced muscle toxicity in vivo: Implications for a targeted FSHD therapy","volume":"20","author":"Wallace","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.omtm.2017.12.005","article-title":"Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD","volume":"8","author":"Wallace","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.omtn.2020.12.004","article-title":"Designed U7 snRNAs inhibit DUX4 expression and improve FSHD-associated outcomes in DUX4 overexpressing cells and FSHD patient myotubes","volume":"23","author":"Rashnonejad","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1096\/fj.201902696","article-title":"DNA aptamers against the DUX4 protein reveal novel therapeutic implications for FSHD","volume":"34","author":"Klingler","year":"2020","journal-title":"FASEB J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.omtn.2020.10.028","article-title":"A Deoxyribonucleic Acid Decoy Trapping DUX4 for the Treatment of Facioscapulohumeral Muscular Dystrophy","volume":"22","author":"Mariot","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature04791","article-title":"Fatality in mice due to oversaturation of cellular microRNA\/short hairpin RNA pathways","volume":"441","author":"Grimm","year":"2006","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"9840","DOI":"10.1093\/nar\/gkaa715","article-title":"Some ASOs that bind in the coding region of mRNAs and induce RNase H1 cleavage can cause increases in the pre-mRNAs that may blunt total activity","volume":"48","author":"Liang","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41573-020-0075-7","article-title":"Advances in oligonucleotide drug delivery","volume":"19","author":"Roberts","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Joubert, R., Mariot, V., Charpentier, M., Concordet, J.P., and Dumonceaux, J. (2020). Gene Editing Targeting the DUX4 Polyadenylation Signal: A Therapy for FSHD?. J. Pers. Med., 11.","DOI":"10.3390\/jpm11010007"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"12598","DOI":"10.1038\/s41598-021-92096-0","article-title":"CRISPR mediated targeting of DUX4 distal regulatory element represses DUX4 target genes dysregulated in Facioscapulohumeral muscular dystrophy","volume":"11","author":"Das","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.omtn.2021.05.020","article-title":"Adenine base editing of the DUX4 polyadenylation signal for targeted genetic therapy in facioscapulohumeral muscular dystrophy","volume":"25","author":"Sikrova","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1136\/jmedgenet-2019-106402","article-title":"Intronic SMCHD1 variants in FSHD: Testing the potential for CRISPR-Cas9 genome editing","volume":"56","author":"Goossens","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/mt.2015.200","article-title":"CRISPR\/dCas9-mediated Transcriptional Inhibition Ameliorates the Epigenetic Dysregulation at D4Z4 and Represses DUX4-fl in FSH Muscular Dystrophy","volume":"24","author":"Himeda","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.tips.2016.02.001","article-title":"Scalpel or Straitjacket: CRISPR\/Cas9 Approaches for Muscular Dystrophies","volume":"37","author":"Himeda","year":"2016","journal-title":"Trends Pharamacol. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.omtm.2020.12.001","article-title":"Targeted epigenetic repression by CRISPR\/dSaCas9 suppresses pathogenic DUX4-fl expression in FSHD","volume":"20","author":"Himeda","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.xphs.2019.10.003","article-title":"Immunogenicity of Cas9 Protein","volume":"109","author":"Mehta","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1056\/NEJMoa2107454","article-title":"CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis","volume":"385","author":"Gillmore","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1038\/s41467-019-09693-x","article-title":"Multifunctional CRISPR-Cas9 with engineered immunosilenced human T cell epitopes","volume":"10","author":"Ferdosi","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nm1398","article-title":"Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer","volume":"12","author":"Brown","year":"2006","journal-title":"Nat. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"674242","DOI":"10.3389\/fimmu.2021.674242","article-title":"Novel Combinatorial MicroRNA-Binding Sites in AAV Vectors Synergistically Diminish Antigen Presentation and Transgene Immunity for Efficient and Stable Transduction","volume":"12","author":"Muhuri","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Kantor, A., McClements, M.E., and MacLaren, R.E. (2020). CRISPR-Cas9 DNA Base-Editing and Prime-Editing. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176240"},{"key":"ref_90","first-page":"14","article-title":"Neuromuscular electrical stimulation promotes development in mice of mature human muscle from immortalized human myoblasts","volume":"6","author":"Sakellariou","year":"2016","journal-title":"Skelet. Muscle"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"113011","DOI":"10.1016\/j.expneurol.2019.113011","article-title":"Muscle xenografts reproduce key molecular features of facioscapulohumeral muscular dystrophy","volume":"320","author":"Mueller","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/rmv.1762","article-title":"Adeno-associated virus (AAV) vectors in gene therapy: Immune challenges and strategies to circumvent them","volume":"23","author":"Hareendran","year":"2013","journal-title":"Rev. Med. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5432","DOI":"10.1038\/s41467-020-19230-w","article-title":"Identification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants","volume":"11","author":"Weinmann","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4919","DOI":"10.1016\/j.cell.2021.08.028","article-title":"Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species","volume":"184","author":"Tabebordbar","year":"2021","journal-title":"Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1172\/JCI68205","article-title":"CpG-depleted adeno-associated virus vectors evade immune detection","volume":"123","author":"Faust","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"eabd3438","DOI":"10.1126\/scitranslmed.abd3438","article-title":"Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses","volume":"13","author":"Chan","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7875","DOI":"10.1128\/JVI.00649-08","article-title":"Adeno-associated virus vector genomes persist as episomal chromatin in primate muscle","volume":"82","author":"Nowrouzi","year":"2008","journal-title":"J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1001\/jamaneurol.2020.1484","article-title":"Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial","volume":"77","author":"Mendell","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3233\/JND-190403","article-title":"AVXS-101 (Onasemnogene Abeparvovec) for SMA1: Comparative Study with a Prospective Natural History Cohort","volume":"6","author":"Kolb","year":"2019","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1089\/hum.2009.182","article-title":"Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: Implications for gene therapy using AAV vectors","volume":"21","author":"Boutin","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"658038","DOI":"10.3389\/fimmu.2021.658038","article-title":"Immunomodulation in Administration of rAAV: Preclinical and Clinical Adjuvant Pharmacotherapies","volume":"12","author":"Chu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/s41598-020-57893-z","article-title":"Capsid-specific removal of circulating antibodies to adeno-associated virus vectors","volume":"10","author":"Bertin","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41591-020-0911-7","article-title":"IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies","volume":"26","author":"Leborgne","year":"2020","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/bit.20562","article-title":"PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization","volume":"92","author":"Lee","year":"2005","journal-title":"Biotechnol. Bioeng."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1038\/sj.gt.3302123","article-title":"Genetic modifications of the adeno-associated virus type 2 capsid reduce the affinity and the neutralizing effects of human serum antibodies","volume":"10","author":"Huttner","year":"2003","journal-title":"Gene Ther."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1182\/blood-2013-01-306647","article-title":"Immune responses to AAV vectors: Overcoming barriers to successful gene therapy","volume":"122","author":"Mingozzi","year":"2013","journal-title":"Blood"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nm1549","article-title":"CD8(+) T-cell responses to adeno-associated virus capsid in humans","volume":"13","author":"Mingozzi","year":"2007","journal-title":"Nat. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"5310","DOI":"10.1172\/JCI70314","article-title":"Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression","volume":"123","author":"Mueller","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"554","DOI":"10.3389\/fimmu.2018.00554","article-title":"Gene Therapy With Regulatory T Cells: A Beneficial Alliance","volume":"9","author":"Biswas","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/mt.2013.268","article-title":"AAV empty capsids: For better or for worse?","volume":"22","author":"Wright","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.ymthe.2020.07.009","article-title":"Broader Implications of Progressive Liver Dysfunction and Lethal Sepsis in Two Boys following Systemic High-Dose AAV","volume":"28","author":"Morales","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.ymthe.2017.03.028","article-title":"Short DNA Hairpins Compromise Recombinant Adeno-Associated Virus Genome Homogeneity","volume":"25","author":"Xie","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.omtm.2020.07.007","article-title":"AAV-Genome Population Sequencing of Vectors Packaging CRISPR Components Reveals Design-Influenced Heterogeneity","volume":"18","author":"Tran","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e0077321","DOI":"10.1128\/JVI.00773-21","article-title":"Improved Genome Packaging Efficiency of Adeno-associated Virus Vectors Using Rep Hybrids","volume":"95","author":"Mietzsch","year":"2021","journal-title":"J. Virol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Echigoya, Y., Trieu, N., Duddy, W., Moulton, H.M., Yin, H., Partridge, T.A., Hoffman, E.P., Kornegay, J.N., Rohret, F.A., and Rogers, C.S. (2021). A Dystrophin Exon-52 Deleted Miniature Pig Model of Duchenne Muscular Dystrophy and Evaluation of Exon Skipping. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313065"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"eabb8920","DOI":"10.1126\/scitranslmed.abb8920","article-title":"Widespread and sustained target engagement in Huntington\u2019s disease minipigs upon intrastriatal microRNA-based gene therapy","volume":"13","author":"Valles","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1007\/s11357-021-00439-6","article-title":"Epigenetic clock and DNA methylation analysis of porcine models of aging and obesity","volume":"43","author":"Schachtschneider","year":"2021","journal-title":"Geroscience"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.4155\/fmc.12.113","article-title":"The development of swine models in drug discovery and development","volume":"4","author":"Swindle","year":"2012","journal-title":"Future Med. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1177\/0300985811402846","article-title":"Swine as models in biomedical research and toxicology testing","volume":"49","author":"Swindle","year":"2012","journal-title":"Vet. Pathol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"293","DOI":"10.3389\/fgene.2015.00293","article-title":"Efficacy of the porcine species in biomedical research","volume":"6","author":"Gutierrez","year":"2015","journal-title":"Front. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13395-020-00227-4","article-title":"Transgenic mice expressing tunable levels of DUX4 develop characteristic facioscapulohumeral muscular dystrophy-like pathophysiology ranging in severity","volume":"10","author":"Jones","year":"2020","journal-title":"Skelet. Muscle"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3233\/JND-140034","article-title":"Multiplex Screen of Serum Biomarkers in Facioscapulohumeral Muscular Dystrophy","volume":"1","author":"Statland","year":"2014","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Portilho, D.M., Alves, M.R., Kratassiouk, G., Roche, S., Magdinier, F., de Santana, E.C., Polesskaya, A., Harel-Bellan, A., Mouly, V., and Savino, W. (2015). miRNA Expression in Control and FSHD Fetal Human Muscle Biopsies. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116853"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.nmd.2016.04.012","article-title":"A cross sectional study of two independent cohorts identifies serum biomarkers for facioscapulohumeral muscular dystrophy (FSHD)","volume":"26","author":"Petek","year":"2016","journal-title":"Neuromuscul. Disord."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Heier, C.R., Zhang, A., Nguyen, N.Y., Tully, C.B., Panigrahi, A., Gordish-Dressman, H., Pandey, S.N., Guglieri, M., Ryan, M.M., and Clemens, P.R. (2020). Multi-Omics Identifies Circulating miRNA and Protein Biomarkers for Facioscapulohumeral Dystrophy. J. Pers. Med., 10.","DOI":"10.3390\/jpm10040236"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"dmm049016","DOI":"10.1242\/dmm.049016","article-title":"Identification of candidate miRNA biomarkers for facioscapulohumeral muscular dystrophy using DUX4-based mouse models","volume":"14","author":"Nunes","year":"2021","journal-title":"Dis. Models Mech."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3233\/JND-210711","article-title":"Identification of Serum Interleukin 6 Levels as a Disease Severity Biomarker in Facioscapulohumeral Muscular Dystrophy","volume":"9","author":"Gros","year":"2022","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Ghasemi, M., Emerson, C.P., and Hayward, L.J. (2022). Outcome Measures in Facioscapulohumeral Muscular Dystrophy Clinical Trials. Cells, 11.","DOI":"10.3390\/cells11040687"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1007\/s00415-003-1116-y","article-title":"Facioscapulohumeral muscular dystrophy. Phenotype-genotype correlation in patients with borderline D4Z4 repeat numbers","volume":"250","author":"Butz","year":"2003","journal-title":"J. Neurol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13023-014-0218-1","article-title":"Low penetrance in facioscapulohumeral muscular dystrophy type 1 with large pathological D4Z4 alleles: A cross-sectional multicenter study","volume":"10","author":"Nguyen","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/ene.13509","article-title":"Clinical and genetic features of patients with facial-sparing facioscapulohumeral muscular dystrophy","volume":"25","author":"He","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e204040","DOI":"10.1001\/jamanetworkopen.2020.4040","article-title":"Phenotypic Variability Among Patients With D4Z4 Reduced Allele Facioscapulohumeral Muscular Dystrophy","volume":"3","author":"Ruggiero","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"102251","DOI":"10.1016\/j.redox.2022.102251","article-title":"Interplay between mitochondrial reactive oxygen species, oxidative stress and hypoxic adaptation in facioscapulohumeral muscular dystrophy: Metabolic stress as potential therapeutic target","volume":"51","author":"Heher","year":"2022","journal-title":"Redox Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/mus.20688","article-title":"Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders","volume":"35","author":"Rodriguez","year":"2007","journal-title":"Muscle Nerve"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"e156125","DOI":"10.1172\/JCI156125","article-title":"Aerobic exercise elicits clinical adaptations in myotonic dystrophy type 1 patients independent of pathophysiological changes","volume":"132","author":"Mikhail","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1136\/jnnp.2007.127571","article-title":"Creatine treatment in muscle disorders: A meta-analysis of randomised controlled trials","volume":"79","author":"Kley","year":"2008","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1080\/14397595.2018.1546357","article-title":"IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review","volume":"29","author":"Ogata","year":"2019","journal-title":"Mod. Rheumatol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1097\/WCO.0000000000000853","article-title":"The elusive promise of myostatin inhibition for muscular dystrophy","volume":"33","author":"Wagner","year":"2020","journal-title":"Curr. Opin. Neurol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"dmm042903","DOI":"10.1242\/dmm.042903","article-title":"Improving translatability of preclinical studies for neuromuscular disorders: Lessons from the TREAT-NMD Advisory Committee for Therapeutics (TACT)","volume":"13","author":"Willmann","year":"2020","journal-title":"Dis. Models Mech."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13148-015-0072-6","article-title":"Individual epigenetic status of the pathogenic D4Z4 macrosatellite correlates with disease in facioscapulohumeral muscular dystrophy","volume":"7","author":"Jones","year":"2015","journal-title":"Clin. Epigenet."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"3685","DOI":"10.1242\/jcs.205427","article-title":"The DUX4 homeodomains mediate inhibition of myogenesis and are functionally exchangeable with the Pax7 homeodomain","volume":"130","author":"Bosnakovski","year":"2017","journal-title":"J. Cell Sci."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/6\/865\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:18:22Z","timestamp":1760138302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/6\/865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,25]]},"references-count":142,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["jpm12060865"],"URL":"https:\/\/doi.org\/10.3390\/jpm12060865","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,25]]}}}