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Title: Ex vivo gene therapy approaches for the treatment of globoid cell leukodystrophy
Author: Visigalli, Ilaria
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2009
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Globoid cell leukodystrophy (GLD) is a rare lysosomal storage disorder (LSD) due to the deficiency of the lysosomal enzyme Galactocerebrosidase (GALC). The enzymatic deficiency results in intracellular storage of undegraded metabolites in the nervous system, leading to progressive dysmyelination. We are testing the feasibility and efficacy of a gene therapy strategy based on hematopoietic stem/progenitor cells (HSPC) and lentiviral vectors (LV) in the murine model of GLD. Differently from what observed with other lysosomal enzymes, GALC gene transfer and expression in HSPC causes apoptosis and functional impairment of the transduced cells due to an inbalance of the intracellular content in bioactive sphingolipids consequent to de novo enzyme expression. Differentiated cells of the myeloid and lymphoid lineages are not affected by GALC expression, suggesting a unique sensitivity of HSPC to enzyme toxicity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available