{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:53:12Z","timestamp":1790779992534,"version":"4.1.0"},"reference-count":84,"publisher":"Rockefeller University Press","issue":"4","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"Netherlands Organisation for Health Research and Development","doi-asserted-by":"publisher","award":["91819613"],"award-info":[{"award-number":["91819613"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organisation for Health Research and Development","doi-asserted-by":"publisher","award":["09150161910168"],"award-info":[{"award-number":["09150161910168"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:p>Nemaline myopathies are the most common form of congenital myopathies. Variants in ACTA1 (NEM3) comprise 15\u201325% of all nemaline myopathy cases. Patients harboring variants in ACTA1 present with a heterogeneous disease course characterized by stable or progressive muscle weakness and, in severe cases, respiratory failure and death. To date, no specific treatments are available. Since NEM3 is an actin-based thin filament disease, we tested the ability of tirasemtiv, a fast skeletal muscle troponin activator, to improve skeletal muscle function in a mouse model of NEM3, harboring the patient-based p.Asp286Gly variant in Acta1. Acute and long-term tirasemtiv treatment significantly increased muscle contractile capacity at submaximal stimulation frequencies in both fast-twitch extensor digitorum longus and gastrocnemius muscle, and intermediate-twitch diaphragm muscle in vitro and in vivo. Additionally, long-term tirasemtiv treatment in NEM3 mice resulted in a decreased respiratory rate with preserved minute volume, suggesting more efficient respiration. Altogether, our data support the therapeutic potential of fast skeletal muscle troponin activators in alleviating skeletal muscle weakness in a mouse model of NEM3 caused by the Acta1:p.Asp286Gly variant.<\/jats:p>","DOI":"10.1085\/jgp.202313471","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T09:23:52Z","timestamp":1708421032000},"update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["<i>Tirasemtiv<\/i>\n                    enhances submaximal muscle tension in an\n                    <i>Acta1<\/i>\n                    :p.Asp286Gly mouse model of nemaline myopathy"],"prefix":"10.1085","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9567-972X","authenticated-orcid":true,"given":"Ricardo A.","family":"Galli","sequence":"first","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam, Physiology 1 , Amsterdam, The Netherlands"},{"name":"Musculoskeletal Health and Tissue Function and Regeneration 2 Amsterdam Movement Sciences, , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7758-9824","authenticated-orcid":true,"given":"Tamara C.","family":"Borsboom","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam, Physiology 1 , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8515-089X","authenticated-orcid":true,"given":"Charlotte","family":"Gineste","sequence":"additional","affiliation":[{"name":"Aix-Marseille University, CNRS, CRMBM 5 , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-0573","authenticated-orcid":true,"given":"Lorenza","family":"Brocca","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00s6t1f81","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pavia 6 Department of Molecular Medicine, , Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8199-4999","authenticated-orcid":true,"given":"Maira","family":"Rossi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00s6t1f81","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pavia 6 Department of Molecular Medicine, , Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3641-7348","authenticated-orcid":true,"given":"Darren T.","family":"Hwee","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cytokinetics Inc. 7 , South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5597-5759","authenticated-orcid":true,"given":"Fady I.","family":"Malik","sequence":"additional","affiliation":[{"name":"Research and Early Development, Cytokinetics Inc. 7 , South San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4960-7490","authenticated-orcid":true,"given":"Roberto","family":"Bottinelli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00s6t1f81","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pavia 6 Department of Molecular Medicine, , Pavia, Italy"},{"name":"IRCCS Mondino Foundation 9 , Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3108-605X","authenticated-orcid":true,"given":"Julien","family":"Gondin","sequence":"additional","affiliation":[{"name":"Aix-Marseille University, CNRS, CRMBM 5 , Marseille, France"},{"name":"Institut NeuroMyoG\u00e8ne, Unit\u00e9 Physiopathologie et G\u00e9n\u00e9tique du Neurone et du Muscle, Universit\u00e9 Claude Bernard Lyon 1, CNRS UMR 5261, INSERM U1315, Universit\u00e9 Lyon 10 , Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1653-1266","authenticated-orcid":true,"given":"Maria-Antonietta","family":"Pellegrino","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00s6t1f81","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Pavia 6 Department of Molecular Medicine, , Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4278-8735","authenticated-orcid":true,"given":"Josine M.","family":"de Winter","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam, Physiology 1 , Amsterdam, The Netherlands"},{"name":"Musculoskeletal Health and Tissue Function and Regeneration 2 Amsterdam Movement Sciences, , Amsterdam, The Netherlands"},{"name":"Heart Failure and Arrhythmias 3 Amsterdam Cardiovascular Sciences, , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8808-4813","authenticated-orcid":true,"given":"Coen A.C.","family":"Ottenheijm","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam, Physiology 1 , Amsterdam, The Netherlands"},{"name":"Pulmonary Hypertension and Atherosclerosis 4 Amsterdam Cardiovascular Sciences, , Amsterdam, The Netherlands"},{"name":"University of Arizona 8 Department of Cellular and Molecular Medicine, , Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"2024031415455765700_bib1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1086\/510402","article-title":"Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2","volume":"80","author":"Agrawal","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2024031415455765700_bib2","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1002\/ana.20157","article-title":"Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutations","volume":"56","author":"Agrawal","year":"2004","journal-title":"Ann. Neurol."},{"key":"2024031415455765700_bib3","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1002\/mus.26017","article-title":"CK-2127107 amplifies skeletal muscle response to nerve activation in humans","volume":"57","author":"Andrews","year":"2018","journal-title":"Muscle Nerve"},{"key":"2024031415455765700_bib4","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3390\/proteomes4020018","article-title":"Role of protein carbonylation in skeletal muscle mass loss associated with chronic conditions","volume":"4","author":"Barreiro","year":"2016","journal-title":"Proteomes"},{"key":"2024031415455765700_bib5","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1164\/rccm.200407-887OC","article-title":"Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease","volume":"171","author":"Barreiro","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2024031415455765700_bib6","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1165\/rcmb.2004-0021OC","article-title":"Protein carbonyl formation in the diaphragm","volume":"32","author":"Barreiro","year":"2005","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2024031415455765700_bib7","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1113\/jphysiol.2014.286740","article-title":"The role of alterations in mitochondrial dynamics and PGC-1\u03b1 over-expression in fast muscle atrophy following hindlimb unloading","volume":"593","author":"Cannavino","year":"2015","journal-title":"J. Physiol."},{"key":"2024031415455765700_bib8","doi-asserted-by":"publisher","first-page":"4615","DOI":"10.1113\/JP278235","article-title":"Fast skeletal muscle troponin activator CK-2066260 increases fatigue resistance by reducing the energetic cost of muscle contraction","volume":"597","author":"Cheng","year":"2019","journal-title":"J. Physiol."},{"key":"2024031415455765700_bib9","doi-asserted-by":"publisher","first-page":"H1009","DOI":"10.1152\/ajpheart.00438.2006","article-title":"Oxidative stress of myosin contributes to skeletal muscle dysfunction in rats with chronic heart failure","volume":"292","author":"Coirault","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2024031415455765700_bib10","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.cell.2017.04.023","article-title":"The logic of the 26S proteasome","volume":"169","author":"Collins","year":"2017","journal-title":"Cell"},{"key":"2024031415455765700_bib11","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1212\/WNL.0000000000001110","article-title":"Congenital myopathies: Natural history of a large pediatric cohort","volume":"84","author":"Colombo","year":"2015","journal-title":"Neurology"},{"key":"2024031415455765700_bib12","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1136\/jmedgenet-2012-101470","article-title":"Troponin activator augments muscle force in nemaline myopathy patients with nebulin mutations","volume":"50","author":"de Winter","year":"2013","journal-title":"J. Med. Genet."},{"key":"2024031415455765700_bib13","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1093\/hmg\/ddab112","article-title":"Acute and chronic tirasemtiv treatment improves in vivo and in vitro muscle performance in actin-based nemaline myopathy mice","volume":"30","author":"de Winter","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"2024031415455765700_bib14","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1172\/JCI124000","article-title":"KBTBD13 is an actin-binding protein that modulates muscle kinetics","volume":"130","author":"de Winter","year":"2020","journal-title":"J. Clin. Invest."},{"key":"2024031415455765700_bib15","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3233\/JND-160200","article-title":"Sarcomere dysfunction in nemaline myopathy","volume":"4","author":"de Winter","year":"2017","journal-title":"J. Neuromuscul. Dis."},{"key":"2024031415455765700_bib16","doi-asserted-by":"publisher","first-page":"239","DOI":"10.3389\/fphys.2015.00239","article-title":"Potential molecular mechanisms underlying muscle fatigue mediated by reactive oxygen and nitrogen species","volume":"6","author":"Debold","year":"2015","journal-title":"Front. Physiol."},{"key":"2024031415455765700_bib17","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S0960-8966(01)00252-8","article-title":"Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy","volume":"12","author":"Donner","year":"2002","journal-title":"Neuromuscul. Disord."},{"key":"2024031415455765700_bib18","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.nmd.2008.09.005","article-title":"Genotype-phenotype correlations in ACTA1 mutations that cause congenital myopathies","volume":"19","author":"Feng","year":"2009","journal-title":"Neuromuscul. Disord."},{"key":"2024031415455765700_bib19","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1093\/cvr\/cvv185","article-title":"Citrullination of myofilament proteins in heart failure","volume":"108","author":"Fert-Bober","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"2024031415455765700_bib20","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1002\/mrm.22386","article-title":"A strictly noninvasive MR setup dedicated to longitudinal studies of mechanical performance, bioenergetics, anatomy, and muscle recruitment in contracting mouse skeletal muscle","volume":"64","author":"Giannesini","year":"2010","journal-title":"Magn. Reson. Med."},{"key":"2024031415455765700_bib21","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.nmd.2012.12.011","article-title":"In vivo and in vitro investigations of heterozygous nebulin knock-out mice disclose a mild skeletal muscle phenotype","volume":"23","author":"Gineste","year":"2013","journal-title":"Neuromuscul. Disord."},{"key":"2024031415455765700_bib22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072294","article-title":"Multimodal MRI and (31)P-MRS investigations of the ACTA1(Asp286Gly) mouse model of nemaline myopathy provide evidence of impaired in vivo muscle function, altered muscle structure and disturbed energy metabolism","volume":"8","author":"Gineste","year":"2013","journal-title":"PLoS One"},{"key":"2024031415455765700_bib23","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/j.ajhg.2013.10.020","article-title":"Identification of KLHL41 mutations implicates BTB-Kelch-mediated ubiquitination as an alternate pathway to myofibrillar disruption in nemaline myopathy","volume":"93","author":"Gupta","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"2024031415455765700_bib24","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1002\/mus.24239","article-title":"Tirasemtiv amplifies skeletal muscle response to nerve activation in humans","volume":"50","author":"Hansen","year":"2014","journal-title":"Muscle Nerve"},{"key":"2024031415455765700_bib25","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1152\/jappl.2001.91.5.2233","article-title":"Nitric oxide impairs Ca2+ activation and slows cross-bridge cycling kinetics in skeletal muscle","volume":"91","author":"Heunks","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"2024031415455765700_bib26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096921","article-title":"Fast skeletal muscle troponin activator tirasemtiv increases muscle function and performance in the B6SJL-SOD1G93A ALS mouse model","volume":"9","author":"Hwee","year":"2014","journal-title":"PLoS One"},{"key":"2024031415455765700_bib27","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1086\/320605","article-title":"Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin gene","volume":"68","author":"Ilkovski","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"2024031415455765700_bib28","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1152\/jappl.1987.63.2.713","article-title":"Patterns of EMG activity of rat plantaris muscle during swimming and other locomotor activities","volume":"63","author":"Jasmin","year":"1987","journal-title":"J. Appl. Physiol."},{"key":"2024031415455765700_bib29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-017-0021-x","article-title":"S-nitrosylation of transglutaminase 2 impairs fatty acid-stimulated contraction in hypertensive cardiomyocytes","volume":"50","author":"Jeong","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"2024031415455765700_bib30","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1086\/303089","article-title":"A novel nemaline myopathy in the Amish caused by a mutation in troponin T1","volume":"67","author":"Johnston","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"2024031415455765700_bib31","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/ana.25144","article-title":"Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1-related nemaline myopathy (NEM3)","volume":"83","author":"Joureau","year":"2018","journal-title":"Ann. Neurol."},{"key":"2024031415455765700_bib32","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.redox.2018.05.011","article-title":"Fatiguing contractions increase protein S-glutathionylation occupancy in mouse skeletal muscle","volume":"17","author":"Kramer","year":"2018","journal-title":"Redox Biol."},{"key":"2024031415455765700_bib33","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s40478-022-01400-0","article-title":"Severe ACTA1-related nemaline myopathy: Intranuclear rods, cytoplasmic bodies, and enlarged perinuclear space as characteristic pathological features on muscle biopsies","volume":"10","author":"Labasse","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"2024031415455765700_bib34","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"2024031415455765700_bib35","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1002\/humu.21059","article-title":"Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1)","volume":"30","author":"Laing","year":"2009","journal-title":"Hum. Mutat."},{"key":"2024031415455765700_bib36","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/ng0195-75","article-title":"A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy","volume":"9","author":"Laing","year":"1995","journal-title":"Nat. Genet."},{"key":"2024031415455765700_bib37","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.nmd.2021.07.012","article-title":"Recent advances in nemaline myopathy","volume":"31","author":"Laitila","year":"2021","journal-title":"Neuromuscul. Disord."},{"key":"2024031415455765700_bib38","doi-asserted-by":"publisher","first-page":"5008","DOI":"10.3390\/ijms20205008","article-title":"Functional characterization of the intact diaphragm in a nebulin-based nemaline myopathy (NM) model-effects of the fast skeletal muscle troponin activator tirasemtiv","volume":"20","author":"Lee","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2024031415455765700_bib39","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1056\/NEJM199712183372503","article-title":"Cellular adaptations in the diaphragm in chronic obstructive pulmonary disease","volume":"337","author":"Levine","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"2024031415455765700_bib40","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/acel.12307","article-title":"Aberrant post-translational modifications compromise human myosin motor function in old age","volume":"14","author":"Li","year":"2015","journal-title":"Aging Cell"},{"key":"2024031415455765700_bib41","doi-asserted-by":"publisher","first-page":"3026","DOI":"10.1021\/acs.jmedchem.0c01412","article-title":"Structural basis of Tirasemtiv activation of fast skeletal muscle","volume":"64","author":"Li","year":"2021","journal-title":"J. Med. Chem."},{"key":"2024031415455765700_bib42","doi-asserted-by":"publisher","first-page":"755","DOI":"10.3390\/antiox11040755","article-title":"The role of oxidative stress in skeletal muscle myogenesis and muscle disease","volume":"11","author":"Lian","year":"2022","journal-title":"Antioxidants"},{"key":"2024031415455765700_bib43","doi-asserted-by":"publisher","first-page":"859313","DOI":"10.3389\/fnagi.2022.859313","article-title":"Alterations of lysine acetylation profile in murine skeletal muscles upon exercise","volume":"14","author":"Liang","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"2024031415455765700_bib44","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1097\/NEN.0b013e318293b1cc","article-title":"Distinct underlying mechanisms of limb and respiratory muscle fiber weaknesses in nemaline myopathy","volume":"72","author":"Lindqvist","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"2024031415455765700_bib45","doi-asserted-by":"publisher","first-page":"219","DOI":"10.3233\/JND-150085","article-title":"A premature stop codon in MYO18B is associated with severe nemaline myopathy with cardiomyopathy","volume":"2","author":"Malfatti","year":"2015","journal-title":"J. Neuromuscul. Dis."},{"key":"2024031415455765700_bib46","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1089\/ars.2009.2818","article-title":"Redox balance and carbonylated proteins in limb and heart muscles of cachectic rats","volume":"12","author":"Marin-Corral","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"2024031415455765700_bib47","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1183\/09031936.00072008","article-title":"Oxidised proteins and superoxide anion production in the diaphragm of severe COPD patients","volume":"33","author":"Marin-Corral","year":"2009","journal-title":"Eur. Respir. J."},{"key":"2024031415455765700_bib48","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.nmd.2003.11.003","article-title":"Functional characterisation of a mutant actin (Met132Val) from a patient with nemaline myopathy","volume":"14","author":"Marston","year":"2004","journal-title":"Neuromuscul. Disord."},{"key":"2024031415455765700_bib49","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.ajhg.2016.11.017","article-title":"Biallelic mutations in MYPN, encoding myopalladin, are associated with childhood-onset, slowly progressive nemaline myopathy","volume":"100","author":"Miyatake","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"2024031415455765700_bib50","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1183\/09031936.93.04050587","article-title":"Human respiratory muscles: Fibre morphology and capillary supply","volume":"4","author":"Mizuno","year":"1991","journal-title":"Eur. Respir. J."},{"key":"2024031415455765700_bib51","doi-asserted-by":"publisher","first-page":"3516","DOI":"10.1093\/brain\/awr274","article-title":"Hypertrophy and dietary tyrosine ameliorate the phenotypes of a mouse model of severe nemaline myopathy","volume":"134","author":"Nguyen","year":"2011","journal-title":"Brain"},{"key":"2024031415455765700_bib52","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1007\/s00109-008-0380-9","article-title":"Thin filament proteins mutations associated with skeletal myopathies: Defective regulation of muscle contraction","volume":"86","author":"Ochala","year":"2008","journal-title":"J. Mol. Med."},{"key":"2024031415455765700_bib53","doi-asserted-by":"publisher","first-page":"9807","DOI":"10.1073\/pnas.1001733107","article-title":"A myopathy-linked tropomyosin mutation severely alters thin filament conformational changes during activation","volume":"107","author":"Ochala","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024031415455765700_bib54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045923","article-title":"Nemaline myopathy-related skeletal muscle \u03b1-actin (ACTA1) mutation, Asp286Gly, prevents proper strong myosin binding and triggers muscle weakness","volume":"7","author":"Ochala","year":"2012","journal-title":"PLoS One"},{"key":"2024031415455765700_bib55","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.jsb.2015.09.008","article-title":"X-ray recordings reveal how a human disease-linked skeletal muscle \u03b1-actin mutation leads to contractile dysfunction","volume":"192","author":"Ochala","year":"2015","journal-title":"J. Struct. Biol."},{"key":"2024031415455765700_bib56","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.jsb.2009.11.013","article-title":"Altered myofilament function depresses force generation in patients with nebulin-based nemaline myopathy (NEM2)","volume":"170","author":"Ottenheijm","year":"2010","journal-title":"J. Struct. Biol."},{"key":"2024031415455765700_bib57","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1073\/pnas.96.5.2305","article-title":"Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy","volume":"96","author":"Pelin","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024031415455765700_bib58","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1113\/jphysiol.2002.027375","article-title":"Orthologous myosin isoforms and scaling of shortening velocity with body size in mouse, rat, rabbit and human muscles","volume":"546","author":"Pellegrino","year":"2003","journal-title":"J. Physiol."},{"key":"2024031415455765700_bib59","doi-asserted-by":"publisher","first-page":"C613","DOI":"10.1152\/ajpcell.00232.2007","article-title":"Functional, structural, and chemical changes in myosin associated with hydrogen peroxide treatment of skeletal muscle fibers","volume":"294","author":"Prochniewicz","year":"2008","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2024031415455765700_bib60","doi-asserted-by":"publisher","first-page":"F1000 Faculty Rev-1921","DOI":"10.12688\/f1000research.16422.1","article-title":"Recent advances in understanding congenital myopathies","volume":"7","author":"Ravenscroft","year":"2018","journal-title":"F1000 Res."},{"key":"2024031415455765700_bib61","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1093\/brain\/awr004","article-title":"Mouse models of dominant ACTA1 disease recapitulate human disease and provide insight into therapies","volume":"134","author":"Ravenscroft","year":"2011","journal-title":"Brain"},{"key":"2024031415455765700_bib62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028699","article-title":"Actin nemaline myopathy mouse reproduces disease, suggests other actin disease phenotypes and provides cautionary note on muscle transgene expression","volume":"6","author":"Ravenscroft","year":"2011","journal-title":"PLoS One"},{"key":"2024031415455765700_bib63","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.ajhg.2013.05.004","article-title":"Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy","volume":"93","author":"Ravenscroft","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"2024031415455765700_bib64","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/nm.2618","article-title":"Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases","volume":"18","author":"Russell","year":"2012","journal-title":"Nat. Med."},{"key":"2024031415455765700_bib65","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1002\/ana.1080","article-title":"Nemaline myopathy: A clinical study of 143 cases","volume":"50","author":"Ryan","year":"2001","journal-title":"Ann. Neurol."},{"key":"2024031415455765700_bib66","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.ajhg.2010.10.020","article-title":"Dominant mutations in KBTBD13, a member of the BTB\/Kelch family, cause nemaline myopathy with cores","volume":"87","author":"Sambuughin","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"2024031415455765700_bib67","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1002\/humu.23385","article-title":"Nemaline myopathy and distal arthrogryposis associated with an autosomal recessive\u00a0TNNT3\u00a0splice variant","volume":"39","author":"Sandaradura","year":"2018","journal-title":"Hum. Mutat."},{"key":"2024031415455765700_bib68","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1007\/s13311-015-0345-y","article-title":"A double-blinded, randomized, placebo-controlled trial to evaluate efficacy, safety, and tolerability of single doses of tirasemtiv in patients with acetylcholine receptor-binding antibody-positive myasthenia gravis","volume":"12","author":"Sanders","year":"2015","journal-title":"Neurotherapeutics"},{"key":"2024031415455765700_bib69","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/S1471-4914(01)02089-5","article-title":"Clinical and genetic heterogeneity in nemaline myopathy: A disease of skeletal muscle thin filaments","volume":"7","author":"Sanoudou","year":"2001","journal-title":"Trends Mol. Med."},{"key":"2024031415455765700_bib70","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"2024031415455765700_bib71","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s10974-019-09519-9","article-title":"Nemaline myopathies: A current view","volume":"40","author":"Sewry","year":"2019","journal-title":"J. Muscle Res. Cell Motil."},{"key":"2024031415455765700_bib72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/21678421.2019.1612922","article-title":"A phase III trial of tirasemtiv as a potential treatment for amyotrophic lateral sclerosis","volume":"0","author":"Shefner","year":"2019","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"2024031415455765700_bib73","doi-asserted-by":"publisher","first-page":"574","DOI":"10.3109\/21678421.2013.822517","article-title":"A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis","volume":"14","author":"Shefner","year":"2013","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"2024031415455765700_bib74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052228","article-title":"Muscle activity and inactivity periods during normal daily life","volume":"8","author":"Tikkanen","year":"2013","journal-title":"PLoS One"},{"key":"2024031415455765700_bib75","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1016\/j.ajpath.2023.06.008","article-title":"Different mouse models of nemaline myopathy harboring Acta1 mutations display differing abnormalities related to mitochondrial biology","volume":"193","author":"Tinklenberg","year":"2023","journal-title":"Am. J. Pathol."},{"key":"2024031415455765700_bib76","doi-asserted-by":"publisher","first-page":"9187","DOI":"10.3390\/ijms22179187","article-title":"Troponin variants in congenital myopathies: How they affect skeletal muscle mechanics","volume":"22","author":"van de Locht","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2024031415455765700_bib77","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.nmd.2022.06.009","article-title":"Respiratory muscle function in patients with nemaline myopathy","volume":"32","author":"van Kleef","year":"2022","journal-title":"Neuromuscul. Disord."},{"key":"2024031415455765700_bib78","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1016\/j.bbamcr.2009.04.004","article-title":"Alpha-Skeletal muscle actin nemaline myopathy mutants cause cell death in cultured muscle cells","volume":"1793","author":"Vandamme","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"2024031415455765700_bib79","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.spen.2011.10.004","article-title":"Nemaline myopathies","volume":"18","author":"Wallgren-Pettersson","year":"2011","journal-title":"Semin. Pediatr. Neurol."},{"key":"2024031415455765700_bib80","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1089\/ars.2011.3909","article-title":"Emerging roles of ROS\/RNS in muscle function and fatigue","volume":"15","author":"Westerblad","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"2024031415455765700_bib81","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1002\/ana.24654","article-title":"Mutation-specific effects on thin filament length in thin filament myopathy","volume":"79","author":"Winter","year":"2016","journal-title":"Ann. Neurol."},{"key":"2024031415455765700_bib82","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1002\/mus.24765","article-title":"Prevalence and phenotypes of congenital myopathy due to \u03b1-actin 1 gene mutations","volume":"53","author":"Witting","year":"2016","journal-title":"Muscle Nerve"},{"key":"2024031415455765700_bib83","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3892\/mmr.2014.2184","article-title":"Clinical and pathological features of patients with nemaline myopathy","volume":"10","author":"Yin","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"2024031415455765700_bib84","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1172\/JCI80057","article-title":"Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy","volume":"125","author":"Yuen","year":"2015","journal-title":"J. Clin. Invest."}],"container-title":["Journal of General Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202313471\/1925628\/jgp_202313471.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202313471\/1925628\/jgp_202313471.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T11:46:49Z","timestamp":1710416809000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/156\/4\/e202313471\/276571\/Tirasemtiv-enhances-submaximal-muscle-tension-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,20]]},"references-count":84,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.202313471","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,20]]},"article-number":"e202313471"}}