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
Related in: MedlinePlus
Mentions: TPP1–/– dogs were maintained until disease had progressed to the defined end stage unless complications unrelated to disease progression necessitated early euthanasia. In a previous study, survival time of eight untreated affected dogs to disease end stage was 44 ± 3 weeks. In the current study, the three TPP1–/– dogs that received vehicle reached end-stage disease requiring euthanasia between 39 and 47 weeks of age (Fig. 1). Dogs that received 4 mg rhTPP1 every other week reached end-stage disease requiring euthanasia between 51 and 57 weeks of age. The dogs that received a 16 mg dose of rhTPP1 survived to between 57 and 67 weeks of age (Fig. 1). However, two of these dogs had to be euthanized at 57 and 63 weeks of age, prior to reaching disease end stage, as the result of meningitis and obstructive hydrocephalus, likely related to foreign body reactions to the CNS delivery catheters after they had been in place for long periods (Butt, 2011).
Affiliation: Mason Eye Institute, University of Missouri School of Medicine, and Department of Bioengineering, University of Missouri, Columbia, Missouri.