Hematopoietic stem cell gene therapy for Niemann-Pick disease and other lysosomal storage diseases

Of the various gene therapy approaches under investigation for the treatmen t of genetic diseases, hematopoietic stem cell-mediated gene therapy has at tracted the most interest. Enriched populations of hematopoietic stem cells can be obtained from diseased individuals, genetically modified to express normal gene products, and then transplanted back into these individuals wi thout the risk of graft versus host disease. Following transplantation and engraftment, hematopoietically-derived cells can repopulate various sites o f pathology and express the normal gene product in vivo. Such a procedure h as been accomplished in several mouse models of human genetics diseases, le ading to partial or complete correction of the disease phenotype, and curre nt efforts are now focused on adapting the success of murine systems to lar ger animals, including man. This review will focus on the use of hematopoie tic stem cell-mediated gene therapy for the treatment of lysosomal storage disorders, and discuss recent data obtained in the laboratory using a murin e knock-out mouse model of Types A and B Niemann-Pick disease (NPD). (C) 19 99 Elsevier Science Ireland Ltd. All rights reserved.