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|Title:||Treatment of canine fucosidosis by intracisternal enzyme infusion|
|Citation:||Experimental Neurology, 2011; 230(2):218-226|
|Publisher:||Academic Press Inc Elsevier Science|
|Gauthami S. Kondagari, Barbara M. King, Peter C. Thomson, Peter Williamson, Peter R. Clements, Maria Fuller, Kim M. Hemsley, John J. Hopwood, Rosanne M. Taylor|
|Abstract:||The blood brain barrier is the major obstacle to treating lysosomal storage disorders of the central nervous system such as canine fucosidosis. This barrier was overcome by three, monthly injections of recombinant canine α-l-fucosidase enzyme were given intracisternally. In dogs treated from 8 weeks of age enzyme reached all areas of central nervous system as well as the cervical lymph node, bone marrow and liver. Brainstem and spinal cord samples from regions adjacent to the injection site had highest enzyme levels (39-73% of normal). Substantial enzyme activity (8.5-20% of normal controls) was found in the superficial brain compared to deeper regions (2.6-5.5% of normal). Treatment significantly reduced the fucosyl-linked oligosaccharide accumulation in most areas of CNS, liver and lymph node. In the surface and deep areas of lumbar spinal cord, oligosaccharide accumulation was corrected (79-80% reduction) to near normal levels (p<0.05). In the spinal meninges (thoracic and lumbar) enzyme activity (35-39% of normal control) and substrate reduction (58-63% affected vehicle treated samples) reached levels similar to those seen in phenotypically normal carriers (p<0.05).The procedure was safe and well-tolerated, treated (average 16%) dogs gained more weight (p<0.05) and there was no antibody formation or inflammatory reaction in plasma and CSF following treatments. The capacity of early ERT to modify progression of biochemical storage in fucosidosis is promising as this disease is currently only amenable to treatment by bone marrow transplantation which entails unacceptably high risks for many patients.|
Lysosomal storage disease
Central nervous system
Intracisternal enzyme replacement therapy
Tandem mass spectrometry
|Rights:||Crown copyright © 2011 Published by Elsevier Inc. All rights reserved.|
|Appears in Collections:||Aurora harvest 5|
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