{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:55:45Z","timestamp":1787237745654,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100013223","name":"PTC Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013223","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aromatic \u029f\u2010amino acid decarboxylase (AADC) deficiency is a rare pediatric neurotransmitter disorder that typically necessitates lifelong care, and that carries a risk of childhood mortality. Eladocagene exuparvovec gene therapy is designed to restore AADC production. Study GT\u2010002 (NCT04903288) is a phase 2, multicenter, open\u2010label trial assessing the pharmacodynamics, safety, and efficacy of eladocagene exuparvovec administered to the putamen bilaterally in pediatric patients with AADC deficiency using a magnetic resonance (MR)\u2010compatible cannula. Patients received eladocagene exuparvovec at 1.8\u2009\u00d7\u200910\n                    <jats:sup>11<\/jats:sup>\n                    vector genomes via the SmartFlow MR\u2010compatible cannula in a single operative session. Endpoints include the change from baseline in cerebrospinal fluid homovanillic acid levels, motor milestone achievement, and safety. Here we report results from 48\u2009weeks of follow\u2010up. Mean (SD) cerebrospinal fluid homovanillic acid levels increased from baseline (22.5 [32.3] nmol\/L;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200913) to week 48 (55.3 [45.6] nmol\/L; change from baseline: 28.3 [13.7] nmol\/L;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0003;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20099), indicating\n                    <jats:italic>de novo<\/jats:italic>\n                    dopamine production. At baseline (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200913), all patients showed severe motor developmental delay; at week 48 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912), nine achieved full head control, four could sit unassisted, two could stand with support, and two could walk independently to a toy. Overall, 260 treatment\u2010emergent adverse events were reported in 13 patients; 259 were deemed unrelated and one likely unrelated to the MR\u2010compatible cannula. No treatment\u2010emergent adverse events led to study withdrawal and no deaths occurred. This study provides further evidence of the favorable pharmacodynamic, efficacy, and safety profile of eladocagene exuparvovec in children with AADC deficiency; intraputaminal administration using an MR\u2010compatible cannula was well tolerated. Study GT\u2010002 (NCT04903288) provides further evidence of the favourable pharmacodynamic, efficacy and safety profile of eladocagene exuparvovec gene therapy in children with AADC deficiency over 48 weeks and demonstrates that intraputaminal administration using an MR\u2010compatible cannula was well tolerated, allowing for real\u2010time MRI confirmation of cannula placement and infusate coverage, and for accurate dosing to the putamen.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70151","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T02:05:12Z","timestamp":1771812312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacodynamics, Efficacy, and Safety of Intraputaminal Eladocagene Exuparvovec Administered to Pediatric Patients With\n                    <scp>Aromatic L\u2010Amino Acid Decarboxylase<\/scp>\n                    Deficiency Using an\n                    <scp>MR<\/scp>\n                    \u2010Compatible Cannula: 48 Weeks of Follow\u2010Up"],"prefix":"10.1002","volume":"49","author":[{"given":"Daniel J.","family":"Curry","sequence":"first","affiliation":[{"name":"Section of Pediatric Neurosurgery, Department of Neurosurgery Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6373-1068","authenticated-orcid":false,"given":"Phillip L.","family":"Pearl","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scellig S. D.","family":"Stone","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9245-6878","authenticated-orcid":false,"given":"Donald L.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Division of Neurology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhakar","family":"Vadivelu","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruria","family":"Ben\u2010Zeev","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Vestal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurosurgery Dartmouth Geisel School of Medicine and Dartmouth Hitchcock Medical Center  Lebanon New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1677-3955","authenticated-orcid":false,"given":"Muhammad","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neurology Duke University Hospital  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Hwei","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Neurology National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010Che","family":"Chou","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery National Taiwan University Hospital  Taipei Taiwan"},{"name":"Department of Traumatology National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zion","family":"Zibly","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Sheba Medical Center  Ramat Gan Israel"},{"name":"Department of Neurosurgery Yale University Medical Center  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lior","family":"Ungar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Sheba Medical Center  Ramat Gan Israel"},{"name":"Department of Neurosurgery Yale University Medical Center  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-4282","authenticated-orcid":false,"given":"Mered","family":"Parnes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neurology and Developmental Neuroscience Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7340-1660","authenticated-orcid":false,"given":"Mariam","family":"Hull","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neurology and Developmental Neuroscience Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Emrick","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neurology and Developmental Neuroscience Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6139-7473","authenticated-orcid":false,"given":"Christian","family":"Werner","sequence":"additional","affiliation":[{"name":"PTC Therapeutics Germany, GmbH  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Krolick","sequence":"additional","affiliation":[{"name":"PTC Therapeutics, Inc.  Warren New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay","family":"Penematsa","sequence":"additional","affiliation":[{"name":"PTC Therapeutics, Inc.  Warren New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Wang","sequence":"additional","affiliation":[{"name":"PTC Therapeutics, Inc.  Warren New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rezwanur","family":"Rahman","sequence":"additional","affiliation":[{"name":"PTC Therapeutics, Inc.  Warren New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Golden","sequence":"additional","affiliation":[{"name":"PTC Therapeutics, Inc.  Warren New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8802-5728","authenticated-orcid":false,"given":"Yin\u2010Hsiu","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Wuh\u2010Liang","family":"Hwu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics National Taiwan University Hospital  Taipei Taiwan"},{"name":"Precision Medical Center, China Medical University Hospital  Taichung City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0522-z"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.2217\/fnl-2022-0012"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003640"},{"key":"e_1_2_12_5_1","unstructured":"Medicines and Healthcare Products Regulatory Agency \u201cUpstaza (Eladocagene Exuparvovec) Solution for Infusion. 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