Document Detail

Enzyme Replacement Therapy Delays Pupillary Light Reflex Deficits in a Canine Model of Late Infantile Neuronal Ceroid Lipofuscinosis.
MedLine Citation:
PMID:  24954537     Owner:  NLM     Status:  Publisher    
Late-infantile neuronal ceroid lipofuscinosis (CLN2) is a hereditary neurological disorder characterized by progressive retinal degeneration and vision loss, cognitive and motor decline, seizures, and pronounced brain atrophy. This fatal pediatric disease is caused by mutations in the CLN2 gene which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Utilizing a TPP1-/- Dachshund model of CLN2, studies were conducted to assess the effects of TPP1 enzyme replacement administered directly to the CNS on disease progression. Recombinant human TPP1 (rhTPP1) or artificial cerebrospinal fluid vehicle was administered to CLN2-affected dogs via infusion into the CSF. Untreated and vehicle treated affected dogs exhibited progressive declines in pupillary light reflexes (PLRs) and electroretinographic (ERG) responses to light stimuli. Studies were undertaken to determine whether CSF administration of rhTPP1 alters progression of the PLR and ERG deficits in the canine model. rhTPP1 administration did not inhibit the decline in ERG responses, as rhTPP1 treated, vehicle treated, and untreated dogs all exhibited similar progressive and profound declines in ERG amplitudes. However, in some of the dogs treated with rhTPP1 there were substantial delays in the appearance and progression of PLR deficits compared with untreated or vehicle treated affected dogs. These findings indicate that CSF administration of TPP1 can attenuate functional impairment of neural pathways involved in mediating the PLR but does not prevent loss of retinal responses detectable with ERG.
Rebecca E H Whiting; Kristina Narfström; Gang Yao; Jacqueline W Pearce; Joan R Coates; Leilani J Castaner; Cheryl A Jensen; Brittanie N Dougherty; Brian R Vuillemenot; Derek Kennedy; Charles A O'Neill; Martin L Katz
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-19
Journal Detail:
Title:  Experimental eye research     Volume:  -     ISSN:  1096-0007     ISO Abbreviation:  Exp. Eye Res.     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370707     Medline TA:  Exp Eye Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
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