Long-term expression of beta-glucuronidase by genetically modified human neural progenitor cells grafted into the mouse central nervous system

Molecular and Cellular Neurosciences
Delphine BuchetJ Mallet

Abstract

Mucopolysaccharidosis type VII (MPS VII) is an inherited disease caused by beta-glucuronidase (beta-glu) deficiency. This deficiency results in the lysosomal accumulation of glycosaminoglycans in all tissues and affects a wide range of organs, including the central nervous system (CNS). Gene transfer is a promising approach to therapy for MPS VII because it allows extensive delivery of the enzyme to the affected tissues. We studied neurotransplantation of primary human cells to supply beta-glucuronidase to the CNS. Human neural progenitor cells (HNPC) were amplified and cotransduced with two lentiviral vectors, one encoding the green fluorescent protein and the other the human beta-glu. We show that these cells strongly expressed both transgenes in culture. When grafted into the mouse striatum, HNPC differentiated into neurons and astrocytes and expressed the two transgenes for at least 6 months. This study therefore paves the way for the treatment of MPS VII by long-term delivery of the appropriate enzyme.

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Citations

Sep 10, 2011·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Lamya S Shihabuddin, Seng H Cheng
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