{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:11:34Z","timestamp":1790964694807,"version":"4.1.0"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"35","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,8,29]]},"abstract":"<jats:p>\n            Menkes disease is an X-linked recessive condition characterized by seizures, failure to thrive, and rapid, progressive neurodegeneration beginning within weeks after birth. Death usually occurs by 3 years of age. The disorder is caused by genetic variants in\n            <jats:italic toggle=\"yes\">ATP7A<\/jats:italic>\n            , an evolutionarily conserved copper transporter that is crucial for normal brain development. The\n            <jats:italic toggle=\"yes\">mottled-brindled<\/jats:italic>\n            mouse recapitulates salient features of the human illness. Affected male mice typically die by 14 postnatal days. We evaluated a single-dose intravenous adeno-associated virus gene therapy approach to deliver working copies of a codon-optimized version of ATP7A to male\n            <jats:italic toggle=\"yes\">mottled-brindled<\/jats:italic>\n            mice. In conjunction with subcutaneous injections of clinical-grade copper histidinate in the first month of life, 95% long-term survival was attained, which was correlated with improvements in serum and brain copper levels, brain neurochemical profiles, somatic growth, and neuromotor function. The notable results support a trial of this treatment combination in affected male newborns with Menkes disease.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adw5612","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T17:58:38Z","timestamp":1756490318000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":9,"title":["Intravenous AAV9-\n            <i>ATP7A<\/i>\n            plus subcutaneous copper histidinate optimizes outcomes in a lethal Menkes disease mouse model"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3649-9996","authenticated-orcid":true,"given":"Lalitha","family":"Venkataraman","sequence":"first","affiliation":[{"name":"Center for Gene Therapy, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9848-9956","authenticated-orcid":true,"given":"Christopher J.","family":"Jeanty","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7617-1662","authenticated-orcid":true,"given":"Tarun","family":"Kaniganti","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."},{"name":"Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8627-8270","authenticated-orcid":true,"given":"Patricia","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Autonomic Medicine Section, Clinical Neurosciences Program, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5709-9940","authenticated-orcid":true,"given":"David S.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Autonomic Medicine Section, Clinical Neurosciences Program, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7522-926X","authenticated-orcid":true,"given":"Stephen G.","family":"Kaler","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."},{"name":"Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"764","article-title":"A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration","volume":"29","author":"Menkes J. 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