Convection perfusion of glucocerebrosidase for neuronopathic Gaucher's disease

Russell R. Lonser, Stuart Walbridge, Gary J. Murray, Michele R. Aizenberg, Alexander Vortmeyer, Johannes M.F.G. Aerts, Roscoe O. Brady, Edward H. Oldfield

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Systemic enzyme replacement for Gaucher's disease has not prevented premature death or severe morbidity in patients with a neuronopathic phenotype, because the enzyme does not cross the blood-brain barrier. We used convection-enhanced delivery for regional distribution of glucocerebrosidase in rat and primate brains and examined its safety and feasibility for neuronopathic Gaucher's disease. Rats underwent intrastriatal infusion and were observed and then sacrificed at 14 hours, 4 days, or 6 weeks. Primates underwent serial magnetic resonance imaging during enzyme perfusion of the right frontal lobe or brainstem, were observed and then sacrificed after infusion completion. Animals underwent histologic and enzymatic tissue analyses. Magnetic resonance imaging revealed perfusion of the primate right frontal lobe or pons with infusate. Enzyme activity was substantially and significantly (p < 0.05) increased in cortex and white matter of the infused frontal lobe and pons compared to control. Immunohistochemistry demonstrated intraneuronal glucocerebrosidase. There was no toxicity. Convection-enhanced delivery can be used to safely perfuse large regions of the brain and brainstem with therapeutic levels of glucocerebrosidase. Patients with neuronopathic Gaucher's disease and similar central nervous system disorders may benefit from this treatment.

Original languageEnglish (US)
Pages (from-to)542-548
Number of pages7
JournalAnnals of Neurology
Volume57
Issue number4
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

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Glucosylceramidase
Gaucher Disease
Convection
Frontal Lobe
Perfusion
Primates
Pons
Enzymes
Brain Stem
Premature Mortality
Magnetic Resonance Angiography
Central Nervous System Diseases
Brain
Blood-Brain Barrier
Immunohistochemistry
Magnetic Resonance Imaging
Morbidity
Phenotype
Safety
Therapeutics

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Lonser, R. R., Walbridge, S., Murray, G. J., Aizenberg, M. R., Vortmeyer, A., Aerts, J. M. F. G., ... Oldfield, E. H. (2005). Convection perfusion of glucocerebrosidase for neuronopathic Gaucher's disease. Annals of Neurology, 57(4), 542-548. https://doi.org/10.1002/ana.20444

Convection perfusion of glucocerebrosidase for neuronopathic Gaucher's disease. / Lonser, Russell R.; Walbridge, Stuart; Murray, Gary J.; Aizenberg, Michele R.; Vortmeyer, Alexander; Aerts, Johannes M.F.G.; Brady, Roscoe O.; Oldfield, Edward H.

In: Annals of Neurology, Vol. 57, No. 4, 01.04.2005, p. 542-548.

Research output: Contribution to journalArticle

Lonser, RR, Walbridge, S, Murray, GJ, Aizenberg, MR, Vortmeyer, A, Aerts, JMFG, Brady, RO & Oldfield, EH 2005, 'Convection perfusion of glucocerebrosidase for neuronopathic Gaucher's disease', Annals of Neurology, vol. 57, no. 4, pp. 542-548. https://doi.org/10.1002/ana.20444
Lonser RR, Walbridge S, Murray GJ, Aizenberg MR, Vortmeyer A, Aerts JMFG et al. Convection perfusion of glucocerebrosidase for neuronopathic Gaucher's disease. Annals of Neurology. 2005 Apr 1;57(4):542-548. https://doi.org/10.1002/ana.20444
Lonser, Russell R. ; Walbridge, Stuart ; Murray, Gary J. ; Aizenberg, Michele R. ; Vortmeyer, Alexander ; Aerts, Johannes M.F.G. ; Brady, Roscoe O. ; Oldfield, Edward H. / Convection perfusion of glucocerebrosidase for neuronopathic Gaucher's disease. In: Annals of Neurology. 2005 ; Vol. 57, No. 4. pp. 542-548.
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