Delivery of therapeutic protein for prevention of neurodegenerative changes: Comparison of different CSF-delivery methods.

Delivery of therapeutic protein for prevention of neurodegenerative changes: Comparison of different CSF-delivery methods. Exp Neurol. 2014 Sep 19; Authors: Marshall NR, Hassiotis S, King B, Rozaklis T, Trim PJ, Duplock SK, Winner LK, Beard H, Snel MF, Jolly RD, Hopwood JJ, Hemsley KM Abstract Injection of lysosomal enzyme into cisternal or ventricular cerebrospinal fluid (CSF) has been carried out in 11 lysosomal storage disorder models, with each study demonstrating reductions in primary substrate and secondary neuropathological changes, and several reports of improved neurological function. Whilst acute studies in mucopolysaccharidosis (MPS) type II mice revealed that intrathecally-delivered enzyme (into thoraco-lumbar CSF) accesses the brain, the impact of longer-term treatment of affected subjects via this route is unknown. This approach is presently being utilized to treat children with MPS types I, II and III. Our aim was to determine the efficacy of repeated intrathecal injection of recombinant human sulfamidase (rhSGSH) on pathological changes in the MPS IIIA dog brain. The outcomes were compared with those in dogs treated via intra-cisternal or ventricular routes. Control dogs received buffer or no treatment. Significant reductions in primary/secondary substrate levels in brain were observed in dogs treated via all routes, although the extent of the reduction differed regionally. Treatment via all CSF access points resulted...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research