{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:59:51Z","timestamp":1793217591086,"version":"4.5.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Childs Nerv Syst"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>We present two clinical cases of frameless, neuronavigated gene therapy with eladocagene exuparvovec for aromatic L-amino acid decarboxylase (AADC) deficiency in pediatric patients, detailing the targeted bilateral microdose delivery of viral vectors into the putamen and highlighting the feasibility and challenges of this approach in managing a rare neurometabolic disorder.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two patients with a confirmed diagnosis of AADCD underwent frameless stereotactic gene therapy. High-resolution 3\u00a0T MRI-guided trajectories were planned for the targeted bilateral putaminal infusion of 0.32\u00a0ml of eladocagene exuparvovec (AAV2-hAADC). The agent was delivered via a SmartFlow Neuro Ventricular Cannula in a \u201cZ-pattern,\u201d retracting the cannula 2\u00a0mm every 9 min to achieve controlled microdosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Accurate frameless drug delivery was achieved in a shorter time than frame-based approaches, with no intraoperative or postoperative complications. One patient showed a small post-ischemic cyst on the 1-month follow-up MRI, without any neurological deficits. Over 2 months, both patients demonstrated reduced oculogyric crises, diminished hyperkinesis, and improved head control, with no significant adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Frameless, neuronavigated gene therapy for AADC deficiency proved both feasible and safe, with early clinical improvements observed in motor function and symptom control. This technique offers a promising alternative to frame-based methods and expands treatment options for this rare neurometabolic disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00381-025-07020-y","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T06:39:56Z","timestamp":1762756796000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Frameless intraputaminal delivery of gene therapy with eladocagene exuparvovec in patients with aromatic L-amino acid decarboxylase deficiency: safe and efficient results"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1376-390X","authenticated-orcid":false,"given":"Roni","family":"Mai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8146-5501","authenticated-orcid":false,"given":"Dmitriy","family":"Reshchikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4835-8047","authenticated-orcid":false,"given":"Vladimir","family":"Popov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9471-7761","authenticated-orcid":false,"given":"Sergey","family":"Gorelikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5020-1180","authenticated-orcid":false,"given":"Ekaterina","family":"Zakharova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2115-985X","authenticated-orcid":false,"given":"Svetlana","family":"Mikhaylova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"7020_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24524-8","author":"TS Pearson","year":"2021","unstructured":"Pearson TS, Gupta N, San Sebastian W et al (2021) Gene therapy for aromatic l-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons. 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J Inherit Metab Dis 47:463\u2013475. https:\/\/doi.org\/10.1002\/jimd.12649","journal-title":"J Inherit Metab Dis"},{"key":"7020_CR4","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.ymthe.2021.11.005","volume":"30","author":"CH Tai","year":"2022","unstructured":"Tai CH, Lee NC, Chien YH et al (2022) Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency. Mol Ther 30:509\u2013518. https:\/\/doi.org\/10.1016\/j.ymthe.2021.11.005","journal-title":"Mol Ther"},{"key":"7020_CR5","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2210555","author":"S Rizzi","year":"2022","unstructured":"Rizzi S, Spagnoli C, Frattini D et al (2022) Clinical features in aromatic L-amino acid decarboxylase (AADC) deficiency: a systematic review. Behav Neurol. https:\/\/doi.org\/10.1155\/2022\/2210555","journal-title":"Behav Neurol"},{"key":"7020_CR6","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0522-z","author":"T Wassenberg","year":"2017","unstructured":"Wassenberg T, Molero-Luis M, Jeltsch K et al (2017) Consensus guideline for the diagnosis and treatment of aromatic L-amino acid decarboxylase (AADC) deficiency. Orphanet J Rare Dis. https:\/\/doi.org\/10.1186\/s13023-016-0522-z","journal-title":"Orphanet J Rare Dis"},{"key":"7020_CR7","doi-asserted-by":"publisher","unstructured":"Hwu WL, Muramatsu SI, Tseng SH, et al (2012) Gene therapy for aromatic L-amino acid decarboxylase deficiency. 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Written informed consent was obtained from the parents of all patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"346"}}