{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:41:19Z","timestamp":1783698079132,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001786","name":"University of Adelaide","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1121522"],"award-info":[{"award-number":["1121522"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sanfilippo syndrome (mucopolysaccharidosis type IIIA; MPS IIIA) is a childhood dementia caused by inherited mutations in the sulfamidase gene. At present, there is no treatment and children with classical disease generally die in their late teens. Intravenous or intra\u2010cerebrospinal fluid (CSF) injection of AAV9\u2010gene replacement is being examined in human clinical trials; evaluation of the impact on brain disease is an intense focus; however, MPS IIIA patients also experience profound, progressive photoreceptor loss, leading to night blindness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To compare the relative efficacy of the two therapeutic approaches on retinal degeneration in MPS IIIA mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Neonatal mice received i.v. or intra\u2010CSF AAV9\u2010sulfamidase or vehicle and after 20\u2009weeks, biochemical and histological evaluation of neuroretina integrity was carried out.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both treatments improved central retinal thickness; however, in peripheral retina, outer nuclear layer thickness and photoreceptor cell length were only significantly improved by i.v. gene replacement. Further, normalization of endo\u2010lysosomal compartment size and microglial morphology was only observed following intravenous gene delivery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Confirmatory studies are needed in adult mice; however, these data indicate that i.v. AAV9\u2010sulfamidase infusion leads to superior outcomes in neuroretina, and cerebrospinal fluid\u2010delivered AAV9 may need to be supplemented with another therapeutic approach for optimal patient quality of life.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14919","type":"journal-article","created":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T04:08:24Z","timestamp":1723262904000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluation of neuroretina following i.v. or intra\u2010<scp>CSF AAV9<\/scp> gene replacement in mice with <scp>MPS IIIA<\/scp>, a childhood dementia"],"prefix":"10.1111","volume":"30","author":[{"given":"Helen","family":"Beard","sequence":"first","affiliation":[{"name":"Childhood Dementia Research Group Flinders Health and Medical Research Institute College of Medicine and Public Health Flinders University  Bedford Park South Australia 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