{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:00:25Z","timestamp":1791392425556,"version":"4.3.3"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>\n                      GNE myopathy (GNEM) is a rare, autosomal recessive disorder caused by mutations in the UDP\u2010N\u2010acetylglucosamine (GlcNAc) 2\u2010epimerase\/N\u2010acetylmannosamine (ManNAc) kinase (\n                      <jats:italic>GNE<\/jats:italic>\n                      ) gene, which encodes a required enzyme for sialic acid (SA) biosynthesis. Reduced SA production is associated with progressive skeletal muscle wasting, but robust molecular biomarkers of SA deficiency and therapeutic restoration remain lacking. As gene therapy for GNEM continues to advance, there is a critical need for biomarkers that enable early, objective assessment of therapeutic response that may precede detectable clinical improvements. Here, we systematically compare a panel of glycan\u2010binding lectins to identify sensitive and robust biomarkers of SA deficiency and restoration in GNEM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated a panel of glycan\u2010binding lectins for differential binding under altered sialylation using fluorescent staining and flow cytometry in a\n                      <jats:italic>GNE\u2010<\/jats:italic>\n                      deficient cell model, followed by fluorescent lectin staining of skeletal muscle biopsies from GNEM and non\u2010GNEM patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Subterminal lectins SBA, PNA, and VVA showed greater sensitivity to hyposialylation than terminal lectins. By flow cytometry, SBA and PNA increased 90.38\u2010 and 50.03\u2010fold, respectively, in\n                      <jats:italic>GNE<\/jats:italic>\n                      \u2010deficient cells and decreased 96.06% and 91.83% following\n                      <jats:italic>GNE<\/jats:italic>\n                      restoration. In GNEM muscle, PNA showed the greatest increase (5.3\u2010fold) and most consistent discrimination from non\u2010GNEM muscle.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>PNA demonstrated the most robust and consistent performance across models, supporting its promise as a biomarker to reflect restoration of sialylation that would occur in skeletal muscle after GNEM gene therapy. Further validation in clinical samples will establish its utility as a pharmacodynamic biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.70404","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:46:37Z","timestamp":1789983997000},"page":"1456-1470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Lectin Staining Biomarkers for\n                    <scp>GNE<\/scp>\n                    Myopathy Gene Therapy"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3603-8516","authenticated-orcid":false,"given":"Kristina M.","family":"Sattler","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology The Ohio State University  Columbus Ohio USA"},{"name":"Dorothy M. Davis Heart and Lung Research Institute, the Ohio State University  Columbus Ohio USA"},{"name":"Wexner Medical Center, The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7814-0685","authenticated-orcid":false,"given":"Brian J.","family":"Paleo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology The Ohio State University  Columbus Ohio USA"},{"name":"Dorothy M. Davis Heart and Lung Research Institute, the Ohio State University  Columbus Ohio USA"},{"name":"Wexner Medical Center, The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie N.","family":"Roth","sequence":"additional","affiliation":[{"name":"Department of Biology Mount St. Joseph University  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara E.","family":"Bradley","sequence":"additional","affiliation":[{"name":"Department of Biology Mount St. Joseph University  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan N.","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Biology Mount St. Joseph University  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0724-0018","authenticated-orcid":false,"given":"Wakako","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP)  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-112X","authenticated-orcid":false,"given":"Ichizo","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP)  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4022-8057","authenticated-orcid":false,"given":"Christoph","family":"Lepper","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology The Ohio State University  Columbus Ohio USA"},{"name":"Dorothy M. 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