CANINE FUCOSIDOSIS - A MODEL FOR RETROVIRAL GENE-TRANSFER INTO HEMATOPOIETIC STEM-CELLS

Severe progressive fatal neurological degeneration occurs in fucosidos is, a storage disease. Bone marrow transplantation into affected dogs has shown that haematopoietic stem cells can provide enzyme producing daughter cells to the central nervous system, altering disease course. This makes canine fucosidosis an ideal large animal model for gene th erapy. Fucosidosis affected allogeneic or autologous canine marrow was transduced ex vivo by cocultivation, then transplanted into fucosidos is affected dogs conditioned with total lymphoid irradiation. The vect ors were Moloney murine leukaemia virus based. Transduction efficiency was increased with multiple cytokines in short term marrow culture. D espite high levels of transduction, proviral sequence was detected 2 m onths post transplant in only one dog. Early or total graft failure oc curred in all transplants. We believe lack of engraftment could be cau sed by differentiation or change of repopulating ability of marrow cel ls occurring with multiple cytokine mixes in culture media. (C) 1997 E lsevier Science B.V.