Nonablative neonatal marrow transplantation attenuates functional and physical defects of beta-glucuronidase deficiency.

Abstract	The toxicity of preparative regimens render neonatal bone marrow transplantation (BMT) for progressive childhood diseases a controversial treatment. Ablative BMT in neonatal mice with or without the lysosomal storage disease mucopolysaccharidosis type VII (MPS VII) show high morbidity and developmental disruption of both brain and bone structure. In this investigation, BMT was performed with a high dose of congenic, normal bone marrow into nonablated newborn mice. Recipients had lifelong, multilineage, peripheral blood chimerism with the donor beta-glucuronidase-positive (GUS(+)) cells that was both well tolerated and therapeutic. Three daily injections of normal adult marrow increased the average life span by at least 6 months and corrected the functional breeding deficits typical of the MPS VII mice. Twelve months after injection, several structural features of femurs were more like that of normal mice than of untreated MPS VII mice. Periosteal circumference and bone cortical thickness were significantly improved in males and cortical density did not differ significantly from values in normal females. Significant reduction of lysosomal glycosaminoglycan storage corresponded directly with GUS enzyme activity and percentage of histochemically GUS(+) cells in visceral organs and hematopoietic tissues such as thymus, spleen, peripheral blood, and bone marrow. By all criteria tested, BMT into neonatal MPS VII mice in the absence of any preparative regimen is a successful therapy.
Authors	B W Soper, M D Lessard, C A Vogler, B Levy, W G Beamer, W S Sly, J E Barker
Journal	Blood (Blood) Vol. 97 Issue 5 Pg. 1498-504 (Mar 01 2001) ISSN: 0006-4971 [Print] United States
PMID	11222399 (Publication Type: Evaluation Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Glucuronidase
Topics	Adult Animals Animals, Newborn Bone Marrow Transplantation (methods, standards) Female Femur (abnormalities, drug effects, pathology) Glucuronidase (deficiency, metabolism, pharmacology) Graft Survival Humans Male Mice Mice, Inbred BALB C Mice, Mutant Strains Mucopolysaccharidosis VII (therapy) Reproduction Tissue Distribution

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