{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:07:28Z","timestamp":1793390848072,"version":"4.5.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    GNE myopathy is a rare, adult-onset, autosomal recessive muscle disorder caused by biallelic pathogenic variants in the\n                    <jats:italic toggle=\"yes\">GNE<\/jats:italic>\n                    gene, which encodes a key enzyme in the biosynthesis of sialic acid. Deficient GNE enzyme activity results in decreased production of sialic acid and subsequent hyposialylation of muscle glycoproteins, ultimately leading to progressive muscle degeneration and characteristic histopathological changes. The disease typically presents with progressive distal muscle weakness while sparing the quadriceps until advanced stages. Advances in molecular biology have significantly clarified the underlying disease mechanisms and revealed genotype\u2013phenotype correlations. Natural history studies, supported by patient registries, have detailed the disease course and identified extra-muscular manifestations such as thrombocytopenia and sleep apnea. Multiple therapeutic strategies are under active investigation, including sialic acid supplementation, antioxidant therapy, and gene therapy. Several clinical trials targeting sialic acid biosynthetic pathways, such as oral N-acetylneuraminic acid, ManNAc, and 6\u2019- sialyllactose, have advanced to late-stage development, culminating in the approval of the N-acetyl-neuraminic acid extended-release tablet in Japan in 2024. Other emerging therapeutic approaches, including antioxidant- and gene-based interventions, are also currently being explored. This review synthesizes the current understanding of the molecular pathogenesis of GNE myopathy and highlights recent advances and future prospects in targeted molecular and therapeutic approaches. The ultimate aim is to foster international collaboration toward the development of innovative and effective treatments for GNE myopathy.\n                  <\/jats:p>","DOI":"10.4103\/aian.aian_837_25","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T17:04:16Z","timestamp":1760375056000},"page":"631-639","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Decoding GNE Myopathy: From Molecular Basis to Therapeutic Advances"],"prefix":"10.4103","volume":"28","author":[{"given":"Wakako","family":"Yoshioka","sequence":"first","affiliation":[{"name":"Department of Neuromuscular Research, National Institute of Neuroscience, Kodaira, Tokyo, Japan"},{"name":"Department of Clinical Genome Analysis, Medical Genome Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research, National Institute of Neuroscience, Kodaira, Tokyo, Japan"},{"name":"Department of Clinical Genome Analysis, Medical Genome Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichizo","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research, National Institute of Neuroscience, Kodaira, Tokyo, Japan"},{"name":"Department of Clinical Genome Analysis, Medical Genome Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"R1-20251112","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1097\/WCO.0000000000001090","article-title":"Recent advances in establishing a cure for GNE myopathy","volume":"35","author":"Yoshioka","year":"2022","journal-title":"Curr Opin Neurol"},{"key":"R2-20251112","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/nm.1956","article-title":"Prophylactic treatment with sialic acid metabolites precludes the development of the myopathic phenotype in the DMRV-hIBM mouse model","volume":"15","author":"Malicdan","year":"2009","journal-title":"Nat Med"},{"key":"R3-20251112","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1093\/brain\/awu210","article-title":"Sialyllactose ameliorates myopathic phenotypes in symptomatic GNE myopathy model mice","volume":"137","author":"Yonekawa","year":"2014","journal-title":"Brain"},{"key":"R4-20251112","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.1007\/s00415-024-12396-z","article-title":"Large phenotypic diversity by genotype in patients with GNE myopathy:10 years after the establishment of a national registry in Japan","volume":"271","author":"Yoshioka","year":"2024","journal-title":"J Neurol"},{"key":"R5-20251112","doi-asserted-by":"crossref","first-page":"e000362","DOI":"10.1136\/bmjno-2022-000362","article-title":"Long-term evaluation parameters in GNE myopathy:A 5-year observational follow-up natural history study","volume":"4","author":"Mori-Yoshimura","year":"2022","journal-title":"BMJ Neurol Open"},{"key":"R6-20251112","doi-asserted-by":"crossref","first-page":"107057","DOI":"10.1016\/j.clineuro.2021.107057","article-title":"Extra-muscular manifestations in GNE myopathy patients:A nationwide repository questionnaire survey in Japan","volume":"212","author":"Yoshioka","year":"2022","journal-title":"Clin Neurol Neurosurg"},{"key":"R7-20251112","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/mus.27451","article-title":"Assessment of thrombocytopenia, sleep apnea, and cardiac involvement in GNE myopathy patients","volume":"65","author":"Mori-Yoshimura","year":"2022","journal-title":"Muscle Nerve"},{"key":"R8-20251112","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0022-510X(81)90067-8","article-title":"Familial distal myopathy with rimmed vacuole and lamellar (myeloid) body formation","volume":"51","author":"Nonaka","year":"1981","journal-title":"J Neurol Sci"},{"key":"R9-20251112","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0022-510X(84)90053-4","article-title":"\u201cRimmed vacuole myopathy\u201d sparing the quadriceps. 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