{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T21:03:15Z","timestamp":1784149395550,"version":"3.55.0"},"reference-count":79,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"803","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,6,18]]},"abstract":"<jats:p>\n            In muscles of patients with Duchenne muscular dystrophy (DMD), expression of extracellular matrix proteases and proteoglycans, including A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) and its substrates versican and fibronectin, is increased. Elevated ADAMTS-5 protease activity results in proinflammatory matrikines, including versikine. Here, we hypothesized that targeting ADAMTS-5 with the small-molecule inhibitor GLPG1972 could decrease dystrophic pathology. Using versikine as a marker of target engagement, we observed a robust reduction in human serum after up to 52 weeks of treatment with GLPG1972, confirming inhibition of ADAMTS-5 catalytic activity. Treatment of C57.muscular dystrophy x-linked (\n            <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n            ) mice with GLPG1972, alone or in combination with the standard-of-care prednisolone, increased forelimb grip strength and force output of diaphragm muscles ex vivo when compared with vehicle treatment, and improvements in function were associated with decreased diaphragm inflammation and fibrosis. Treatment of C57.\n            <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n            mice with prednisolone also decreased diaphragm inflammation; however, grip strength, diaphragm force output, and fibrosis did not significantly differ from vehicle treatment. In D2.\n            <jats:italic toggle=\"yes\">mdx<\/jats:italic>\n            mice, GLPG1972 improved forelimb grip strength and wire hang time compared with vehicle. Furthermore, GLPG1972 increased the strength of fast tibialis anterior muscles in situ and slow soleus muscles ex vivo, and this was associated with decreased inflammation, sarcolemma damage, and fibronectin deposition as assessed by immunohistochemistry. Together, these findings position ADAMTS-5 inhibition with GLPG1972 for further study as a disease-modifying strategy for DMD that may achieve both anti-inflammatory and antifibrotic effects on muscle, resulting in improved contractile function.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.ado2112","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T18:00:52Z","timestamp":1750269652000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["ADAMTS-5 inhibition reduces muscle inflammation and fibrosis and improves function in mouse models of Duchenne muscular dystrophy"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0928-9971","authenticated-orcid":true,"given":"John","family":"Dulos","sequence":"first","affiliation":[{"name":"Galapagos B.V., Oegstgeest 2342, Netherlands."},{"name":"Alesta Therapeutics, Leiden 2333, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1851-896X","authenticated-orcid":true,"given":"Danielle A.","family":"Debruin","sequence":"additional","affiliation":[{"name":"Department of Medicine\u2013Western Health, Melbourne Medical School, University of Melbourne, Melbourne, Victoria 3021, Australia."},{"name":"Institute for Health and Sport (IHeS), Victoria University, Melbourne 3011, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"van der Aar","sequence":"additional","affiliation":[{"name":"Galapagos B.V., Oegstgeest 2342, Netherlands."},{"name":"Creative Research Solutions, Hoeilaart 1560, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9506-4565","authenticated-orcid":true,"given":"Venkata Bala Sai","family":"Chaitanya","sequence":"additional","affiliation":[{"name":"Department of Medicine\u2013Western Health, Melbourne Medical School, University of Melbourne, Melbourne, Victoria 3021, Australia."},{"name":"Institute for Health and Sport (IHeS), Victoria University, Melbourne 3011, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2780-408X","authenticated-orcid":true,"given":"Lola","family":"Lecru","sequence":"additional","affiliation":[{"name":"Galapagos B.V., Oegstgeest 2342, Netherlands."},{"name":"Domain Therapeutics, Illkirch-Graffenstaden 67400, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Campelj","sequence":"additional","affiliation":[{"name":"Department of Medicine\u2013Western Health, Melbourne Medical School, University of Melbourne, Melbourne, Victoria 3021, Australia."},{"name":"Institute for Health and Sport (IHeS), Victoria University, Melbourne 3011, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9142-0841","authenticated-orcid":true,"given":"Alex Bernard","family":"Addinsall","sequence":"additional","affiliation":[{"name":"Department of Medicine\u2013Western Health, Melbourne Medical School, University of Melbourne, Melbourne, Victoria 3021, Australia."},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen 2200, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1000-1707","authenticated-orcid":true,"given":"Nicole","family":"Stupka","sequence":"additional","affiliation":[{"name":"Department of Medicine\u2013Western Health, Melbourne Medical School, University of Melbourne, Melbourne, Victoria 3021, Australia."},{"name":"Institute for Health and Sport (IHeS), Victoria University, Melbourne 3011, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181aa31c2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.35.4.451"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abp8964"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32160-8"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep17014"},{"key":"e_1_3_2_7_2","first-page":"353","article-title":"Expression profiling in exercised mdx suggests a role for extracellular proteins in the dystrophic muscle immune response","volume":"29","author":"Coles C. 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