Injection of recombinant human sulfamidase into the CSF via the cerebellomedullary cistern in MPS IIIA mice

Hemsley, Kim M.; King, Barbara; Hopwood, John J.

doi:10.1016/j.ymgme.2006.10.005

Cited by 83 publications

(100 citation statements)

References 41 publications

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“…The progression of vacuolar changes quantified in our fucosidosis study have not been systematically described in other LSD models, so information on the rate of progression in different regions of the CNS is not available for comparison. However, a recent study of MPS IIIA mice reported the rate of progression of vacuolation in CNS from birth to 20 weeks using a qualitative method of assessment [24] .…”

Section: Discussionmentioning

confidence: 99%

Canine Fucosidosis: A Neuroprogressive Disorder

Kondagari

Ramanathan²,

Taylor³

2011

Neurodegener Dis

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The lysosomal storage disease, canine fucosidosis, is caused by the absence of the lysosomal enzyme canine α-L-fucosidase with storage of undegraded fucose-rich material in different organs. Canine fucosidosis is a severe, progressive, fatal neurological disease which results in death or euthanasia and is the only available animal model for this human disease. We analysed the progressive neuropathology from birth to severe clinical disease and related this to the clinical signs. At birth no vacuolation was observed in fucosidosis brain; however, a complex storage presence with vacuolation was well established by 4 months of age, before the clinical signs of motor dysfunction which occurred at 10–12 months of age. Purkinje cell loss, neuronal loss, gliosis, perivascular storage and demyelination accompanied disease progression. Increased vacuolation (15.3-fold increase compared to controls) coincided with advanced motor and mental deterioration in late-stage disease. Significant loss of myelin commenced early, with greatest impact in the cerebellum, and was severe in late disease (1.6- to 1.9-fold decrease) compared to controls (p < 0.05) contributing to clinical signs of motor and mental dysfunction. This detailed description and quantification of the CNS pathology in canine fucosidosis will inform monitoring of the onset, progression and response of this disease to therapy.

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Section: Discussionmentioning

confidence: 99%

Canine Fucosidosis: A Neuroprogressive Disorder

Kondagari

Ramanathan²,

Taylor³

2011

Neurodegener Dis

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“…For adult-injected mice, 6-week-old MPS-IIIA and unaffected mice received bilateral injections into the brain parenchyma (Savas et al, 2004) or cerebrospinal fluid (Hemsley et al, 2007) using established methods.…”

Section: Intracranial Injections Tissue Collection and Antibody Titementioning

confidence: 99%

“…While intra-cerebrospinal fluid delivery of recombinant human SGSH (rhSGSH) is an effective means of restoring enzyme activity and ameliorating pathological and clinical symptoms in MPS-IIIA mice (Hemsley et al, 2007(Hemsley et al, , 2009, alternate strategies that allow life-long treatment from a single intervention would be of considerable value. Gene transfer vectors derived from common human pathogens may show limited longevity and efficacy in patients due to the high frequency of memory immunity against these vectors (Chirmule et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Helper-dependent canine adenovirus vector-mediated transgene expression in a neurodegenerative lysosomal storage disorder

Lau

Rozaklis

Ibanes

et al. 2012

Gene

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“…MPS-I dogs treated intrathecally with recombinant human iduronidase developed serum and CSF antibodies against the enzyme, as well as meningitis (15,16). Similarly, intrathecally treated MPS-IIIA dogs developed antibodies against recombinant human sulfamidase, as well as meningitis (23), whereas MPS-IIIA mice treated with repeated IT-INJs of the same enzyme developed circulating antibodies without meningitis or adverse reactions (24)(25)(26). The small, focal, Wallerian-type degeneration observed near the site of IT-INJ in most intrathecally treated cats, irrespective of presence or absence of polysorbate-80, was attributed to mild iatrogenic trauma produced during IT-INJ, as previously reported (14), again highlighting the importance of a good injection technique (14).…”

Section: Articlesmentioning

confidence: 99%