{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:19:22Z","timestamp":1791001162405,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T00:00:00Z","timestamp":1402963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"DOI":"10.13039\/100005468","name":"Batten Disease Support and Research Association","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/100005468","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:p>Using a canine model of classical late\u2010infantile neuronal ceroid lipofuscinosis (CLN2 disease), a study was conducted to evaluate the potential pharmacological activity of recombinant human tripeptidyl peptidase\u20101 (rhTPP1) enzyme replacement therapy administered directly to the cerebrospinal fluid (CSF). CLN2 disease is a hereditary neurodegenerative disorder resulting from mutations in <jats:italic>CLN2<\/jats:italic>, which encodes the soluble lysosomal enzyme tripeptidyl peptidase\u20101 (TPP1). Infants with mutations in both <jats:italic>CLN2<\/jats:italic> alleles develop normally but in the late\u2010infantile\/early\u2010childhood period undergo progressive neurological decline accompanied by pronounced brain atrophy. The disorder, a form of Batten disease, is uniformly fatal, with clinical signs starting between 2 and 4 years of age and death usually occurring by the early teenage years. Dachshunds homozygous for a null mutation in the canine ortholog of <jats:italic>CLN2<\/jats:italic> (<jats:italic>TPP1)<\/jats:italic> exhibit a similar disorder that progresses to end stage at 10.5\u201311 months of age. Administration of rhTPP1 via infusion into the CSF every other week, starting at approximately 2.5 months of age, resulted in dose\u2010dependent significant delays in disease progression, as measured by delayed onset of neurologic deficits, improved performance on a cognitive function test, reduced brain atrophy, and increased life span. Based on these findings, a clinical study evaluating the potential therapeutic value of rhTPP1 administration into the CSF of children with CLN2 disease has been initiated. \u00a9 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23423","type":"journal-article","created":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T17:22:54Z","timestamp":1403025774000},"page":"1591-1598","source":"Crossref","is-referenced-by-count":97,"title":["Enzyme replacement therapy attenuates disease progression in a canine model of late\u2010infantile neuronal ceroid lipofuscinosis (<scp>CLN<\/scp>2 disease)"],"prefix":"10.1002","volume":"92","author":[{"given":"Martin L.","family":"Katz","sequence":"first","affiliation":[{"name":"Mason Eye Institute, University of Missouri School of Medicine, and Department of Bioengineering, University of Missouri Columbia Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan R.","family":"Coates","sequence":"additional","affiliation":[{"name":"University of Missouri College of Veterinary Medicine Columbia Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Sibigtroth","sequence":"additional","affiliation":[{"name":"University of Missouri College of Veterinary Medicine Columbia Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob D.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Mason Eye Institute, University of Missouri School of Medicine, and Department of Bioengineering, University of Missouri Columbia Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Carpentier","sequence":"additional","affiliation":[{"name":"University of Missouri College of Veterinary Medicine Columbia Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney M.","family":"Young","sequence":"additional","affiliation":[{"name":"University of Missouri College of Veterinary Medicine Columbia Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred A.","family":"Wininger","sequence":"additional","affiliation":[{"name":"University of Missouri College of Veterinary Medicine Columbia Missouri"},{"name":"Veterinary Specialty Services Manchester Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Kennedy","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc. Novato California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Vuillemenot","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc. Novato California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"O'Neill","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc. 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