Autologous transplantation of retrovirally transduced bone marrow or neonatal blood cells into cats can lead to long-term engraftment in the absence of myeloablation

Autologous transplantation of retrovirally transduced bone marrow (B-M) or neonatal blood cells was carried out on eight cats (ranging in age from 2 w eeks to 12 months) with mucopolysaccharidosis type VI (MPS VI). The transdu cing vector contained the full-length cDNA encoding human arylsulfatase B ( hASB), the enzymatic activity deficient in this lysosomal storage disorder. Following transplantation, the persistence of transduced cells and enzymat ic expression were monitored for more than 2 years. Five of the cats receiv ed no myeloablative preconditioning, two cats received 370-390 cGy of total body irradiation (TBI), and one cat received 190 cGy TBI. Evidence of tran sduced cells, as judged by enzymatic activity and PCR defection of the prov irus, was demonstrated in granulocytes, lymphocytes, or BM cells of the tre ated animals up to 31 months after transplantation. Radiation preconditioni ng was not required to achieve these results, nor were they dependent on th e recipient's age. However, despite the long-term persistence of transduced cells, the levels of ASB activity in the transplanted animals was low, and no clinical improvements were defected. These data provide evidence for th e long-term persistence of retrovirally transduced feline hematopoietic cel ls, and further documentation that engraftment of transduced cells can be a chieved in the absence of myeloablation. Consistent with previous bone marr ow transplantation studies, these results also suggest that to achieve clin ical improvement of IMPS VI, particularly in the skeletal system, high-leve l expression of ASB must be achieved in the treated animals and improved te chniques for targeting the expressed enzyme to specific sites of pathology (eg chondrocytes) must be developed.