Treatment of murine mucopolysaccharidosis type VII by syngeneic bone marrow transplantation in neonates.

摘要: BACKGROUND Bone marrow transplantation (BMT) proved an effective therapy for murine mucopolysaccharidosis type VII (MPS VII) in adult gusmps/gusmps mice with well developed clinical and pathologic characteristics of the disease. MPS transplanted as adults had a marked decrease lysosomal storage material many organs, although not skeleton brain (1). Since untreated newborn appear normal have minimal detectable microscopically, we postulated that BMT might prevent subsequent accumulation material. EXPERIMENTAL DESIGN One-day-old mutant phenotypically were exposed to 2, 4, 6 8 Gray then injected intravenously syngeneic bone cells from homozygous females. Transplanted examined biochemically microscopically at 10 weeks months age. RESULTS Newborn receiving lived longer than mutants, less severe facial dysmorphism, better mobility. beta-Glucuronidase activity liver, spleen, kidney increased increasing radiation dose. The secondary elevations alpha-galactosidase beta-hexosaminidase observed VII, significantly reduced liver spleen all groups. Treated mutants histologic evidence disease bones, joints periarticular tissue compared mutants. Neonatal also leptomeninges, ependyma retinal pigment epithelium caused slight neuronal high Radiation dose dependent cerebellar dysplasia long growth retardation was when initiated but animals adults. CONCLUSIONS is more it performed birth rather Alternate means ablating host hematopoietic stem should be employed pretreatment due side effects on newborns.