Enzyme replacement therapy attenuates disease progression in a canine model of late-infantile neuronal ceroid lipofuscinosis (CLN2 disease).
Bottom Line: 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.Administration of rhTPP1 via infusion into the CSF every other week, starting at approximately 2.5 months of age, resulted in dose-dependent 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.
Affiliation: Mason Eye Institute, University of Missouri School of Medicine, and Department of Bioengineering, University of Missouri, Columbia, Missouri.Show MeSH
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Mentions: To determine whether administration of rhTPP1 to the CSF delayed the onset and progression of clinical disease signs, dogs in this study were assessed for neurological abnormalities on a weekly basis. TPP1+/+ dogs all remained neurologically normal throughout the duration of the study. Among vehicle-treated TPP1–/– dogs, an array of neurological deficits became apparent starting between 32 and 38 weeks of age (Fig. 2). These deficits worsened and eventually became so severe that euthanasia was necessary. Euthanasia was performed at the same disease stage based on neurological status in all dogs except when dogs developed complications unrelated to the disease that necessitated early euthanasia as described above.
Affiliation: Mason Eye Institute, University of Missouri School of Medicine, and Department of Bioengineering, University of Missouri, Columbia, Missouri.