Hematopoietic stem cell gene therapy in Hurler syndrome, globoid cell leukodystrophy, metachromatic leukodystrophy and X-adrenoleukodystrophy.
Hurler syndrome, metachromatic leukodystrophy, globoid-cell leukodystrophy (Krabbe's disease) and X-linked adrenoleukodystrophy are inherited diseases of the CNS that can be cured or arrested by allogeneic hematopoietic stem-cell transplantation (HSCT). Despite significant progress in medical procedures and the availability of banked umbilical cord blood, HSCT is still associated with significant risks of graft failure or GVHD that can lead to death. Transplantation of autologous hematopoietic stem cells genetically modified to express the missing protein may circumvent the majority of the problems associated with allogeneic HSCT. Promising in concept, these strategies are now at a stage to be tested in phase I/II clinical trials to assess safety and potential efficacy.
Cartier
Nathalie
N
INSERM U745 and University René Descartes Paris5, Hôpital Saint-Vincent de Paul, Paris, France.
Aubourg
Patrick
P
D000326:Adrenoleukodystrophy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D036101:Cord Blood Stem Cell Transplantation; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D007966:Leukodystrophy, Metachromatic / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D008059:Mucopolysaccharidosis I / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous