{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:42:21Z","timestamp":1792460541208,"version":"4.5.0"},"reference-count":38,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"765","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,9,18]]},"abstract":"<jats:p>\n            Muscle-specific kinase (MuSK) is essential for the formation, function, and preservation of neuromuscular synapses. Activation of MuSK by a MuSK agonist antibody may stabilize or improve the function of the neuromuscular junction (NMJ) in patients with disorders of the NMJ, such as congenital myasthenia (CM). Here, we generated and characterized ARGX-119, a first-in-class humanized agonist monoclonal antibody specific for MuSK, that is being developed for treatment of patients with neuromuscular diseases. We performed in vitro ligand-binding assays to show that ARGX-119 binds with high affinity to the Frizzled-like domain of human, nonhuman primate, rat, and mouse MuSK, without off-target binding, making it suitable for clinical development. Within the Fc region, ARGX-119 harbors L234A and L235A mutations to diminish potential immune-activating effector functions. Its mode of action is to activate MuSK, without interfering with its natural ligand neural Agrin, and cluster acetylcholine receptors in a dose-dependent manner, thereby stabilizing neuromuscular function. In a mouse model of\n            <jats:italic>DOK7<\/jats:italic>\n            CM, ARGX-119 prevented early postnatal lethality and reversed disease relapse in adult\n            <jats:italic>Dok7<\/jats:italic>\n            CM mice by restoring neuromuscular function and reducing muscle weakness and fatigability in a dose-dependent manner. Pharmacokinetic studies in nonhuman primates, rats, and mice revealed a nonlinear PK behavior of ARGX-119, indicative of target-mediated drug disposition and in vivo target engagement. On the basis of this proof-of-concept study, ARGX-119 has the potential to alleviate neuromuscular diseases hallmarked by impaired neuromuscular synaptic function, warranting further clinical development.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.ado7189","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T17:59:01Z","timestamp":1726682341000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":34,"title":["ARGX-119 is an agonist antibody for human MuSK that reverses disease relapse in a mouse model of congenital myasthenic syndrome"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0829-6128","authenticated-orcid":true,"given":"Roeland","family":"Vanhauwaert","sequence":"first","affiliation":[{"name":"argenx, 9052 Zwijnaarde, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Oury","sequence":"additional","affiliation":[{"name":"Helen L. and Martin S. Kimmel Center for Biology and Medicine at Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, NY 10016, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhardt","family":"Vankerckhoven","sequence":"additional","affiliation":[{"name":"argenx, 9052 Zwijnaarde, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3476-6437","authenticated-orcid":true,"given":"Christophe","family":"Steyaert","sequence":"additional","affiliation":[{"name":"argenx, 9052 Zwijnaarde, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1568-5942","authenticated-orcid":true,"given":"Stine Marie","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7268-9818","authenticated-orcid":true,"given":"Dana L. E.","family":"Vergoossen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0685-1810","authenticated-orcid":true,"given":"Christa","family":"Kneip","sequence":"additional","affiliation":[{"name":"argenx, 9052 Zwijnaarde, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1890-9381","authenticated-orcid":true,"given":"Leah","family":"Santana","sequence":"additional","affiliation":[{"name":"Helen L. and Martin S. Kimmel Center for Biology and Medicine at Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, NY 10016, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Lim","sequence":"additional","affiliation":[{"name":"argenx, 9052 Zwijnaarde, Belgium."},{"name":"Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8427-9090","authenticated-orcid":true,"given":"Jaap J.","family":"Plomp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2032-5537","authenticated-orcid":true,"given":"Roy","family":"Augustinus","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5473-4358","authenticated-orcid":true,"given":"Shohei","family":"Koide","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA."},{"name":"Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9152-9978","authenticated-orcid":true,"given":"Christophe","family":"Blanchetot","sequence":"additional","affiliation":[{"name":"argenx, 9052 Zwijnaarde, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ulrichts","sequence":"additional","affiliation":[{"name":"argenx, 9052 Zwijnaarde, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6082-5042","authenticated-orcid":true,"given":"Maartje G.","family":"Huijbers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, Netherlands."},{"name":"Department of Neurology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Silence","sequence":"additional","affiliation":[{"name":"argenx, 9052 Zwijnaarde, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3550-6891","authenticated-orcid":true,"given":"Steven J.","family":"Burden","sequence":"additional","affiliation":[{"name":"Helen L. and Martin S. Kimmel Center for Biology and Medicine at Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, NY 10016, USA."},{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, 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