{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:17:41Z","timestamp":1792815461021,"version":"4.5.0"},"reference-count":78,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is a progressive muscle\u2010wasting disease caused by mutations in the dystrophin gene, which leads to structural instability of the dystrophin\u2013glycoprotein\u2010complex with subsequent muscle degeneration. In addition, muscle inflammation has been implicated in disease progression and therapeutically addressed with glucocorticosteroids. These have numerous adverse effects. Treatment with human immunoglobulin G (IgG) improved clinical and para\u2010clinical parameters in the early disease phase in the well\u2010established <jats:italic>mdx<\/jats:italic> mouse model. The aim of the present study was to confirm the efficacy of IgG in a long\u2010term pre\u2010clinical study in <jats:italic>mdx<\/jats:italic> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IgG (2 g\/kg body weight) or NaCl solution as control was administered monthly over 18 months by intraperitoneal injection in <jats:italic>mdx<\/jats:italic> mice beginning at 3 weeks of age. Several clinical outcome measures including endurance, muscle strength, and echocardiography were assessed. After 18 months, the animals were sacrificed, blood was collected for analysis, and muscle samples were obtained for <jats:italic>ex vivo<\/jats:italic> muscle contraction tests, quantitative PCR, and histology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IgG significantly improved the daily voluntary running performance (1.9 m more total daily running distance, <jats:italic>P<\/jats:italic> &lt; 0.0001) and slowed the decrease in grip strength by 0.1 mN, (<jats:italic>P<\/jats:italic> = 0.018). IgG reduced fatigability of the diaphragm (improved ratio to maximum force by 0.09 \u00b1 0.04, <jats:italic>P<\/jats:italic> = 0.044), but specific tetanic force remained unchanged in the <jats:italic>ex vivo<\/jats:italic> muscle contraction test. Cardiac function was significantly better after IgG, especially fractional area shortening (<jats:italic>P<\/jats:italic> = 0.012). These results were accompanied by a reduction in cardiac fibrosis and the infiltration of T cells (<jats:italic>P<\/jats:italic> = 0.0002) and macrophages (<jats:italic>P<\/jats:italic> = 0.0027). In addition, treatment with IgG resulted in a significant reduction of the infiltration of T cells (<jats:italic>P<\/jats:italic> \u2264 0.036) in the diaphragm, gastrocnemius, quadriceps, and a similar trend in tibialis anterior and macrophages (<jats:italic>P<\/jats:italic> \u2264 0.045) in gastrocnemius, quadriceps, tibialis anterior, and a similar trend in the diaphragm, as well as a decrease in myopathic changes as reflected by a reduced central nuclear index in the diaphragm, tibialis anterior, and quadriceps (<jats:italic>P<\/jats:italic> \u2264 0.002 in all).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study underscores the importance of an inflammatory contribution to the disease progression of DMD. The data demonstrate the long\u2010term efficacy of IgG in the <jats:italic>mdx<\/jats:italic> mouse. IgG is well tolerated by humans and could preferentially complement gene therapy in DMD. The data call for a clinical trial with IgG in DMD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12569","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T01:25:36Z","timestamp":1590024336000},"page":"1018-1031","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Long\u2010term human IgG treatment improves heart and muscle function in a mouse model of Duchenne muscular dystrophy"],"prefix":"10.1002","volume":"11","author":[{"given":"Jana","family":"Zsch\u00fcntzsch","sequence":"first","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia Vanessa","family":"Jouvenal","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen  G\u00f6ttingen 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