title: Autologous transplantation of retrovirally transduced bone marrow or neonatal blood cells into cats can lead to long-term engraftment in the absence of myeloablation.
abstract: Autologous transplantation of retrovirally transduced bone marrow (BM) or neonatal blood cells was carried out on eight cats (ranging in age from 2 weeks to 12 months) with mucopolysaccharidosis type VI (MPS VI). The transducing 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 enzymatic expression were monitored for more than 2 years. Five of the cats received no myeloablative preconditioning, two cats received 370-390 cGy of total body irradiation (TBI), and one cat received 190 cGy TBI. Evidence of transduced cells, as judged by enzymatic activity and PCR detection of the provirus, was demonstrated in granulocytes, lymphocytes, or BM cells of the treated animals up to 31 months after transplantation. Radiation preconditioning was not required to achieve these results, nor were they dependent on the 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 detected. These data provide evidence for the long-term persistence of retrovirally transduced feline hematopoietic cells, and further documentation that engraftment of transduced cells can be achieved in the absence of myeloablation. Consistent with previous bone marrow transplantation studies, these results also suggest that to achieve clinical improvement of MPS VI, particularly in the skeletal system, high-level expression of ASB must be achieved in the treated animals and improved techniques for targeting the expressed enzyme to specific sites of pathology (e.g. chondrocytes) must be developed.
authors.affiliation: Department of Human Genetics, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Simonaro
authors.forename: M E
authors.initials: ME
authors.lastname: Haskins
authors.forename: J L
authors.initials: JL
authors.lastname: Abkowitz
authors.forename: D A
authors.initials: DA
authors.lastname: Brooks
authors.forename: J J
authors.initials: JJ
authors.lastname: Hopwood
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: E H
authors.initials: EH
authors.lastname: Schuchman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016026:Bone Marrow Transplantation; D002415:Cats; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D009087:Mucopolysaccharidosis VI / Q000628:therapy*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D014162:Transfection / Q000379:methods*; D014182:Transplantation, Autologous
chemical_list: D020051:N-Acetylgalactosamine-4-Sulfatase