BONE-MARROW TRANSPLANTATION IN NEWBORN RATS WITH MUCOPOLYSACCHARIDOSIS TYPE-VI - BIOCHEMICAL, PATHOLOGICAL, AND CLINICAL FINDINGS

Background. Mucopolysaccharidosis type VI (MPS VI) is the lysosomal st orage disorder caused by the deficient activity of arylsulfatase B (AS B). In this study, we evaluated bone marrow transplantation (BRIT) for the treatment of RIBS VI and the effects of irradiation on the surviv al and engraftment of bone marrow-transplanted neonatal rats. Methods. One- to 2-day-old MPS VI rats were injected with normal bone marrow a fter irradiation with 200, 400, or 800 cGy. Ninety percent of the anim als receiving a single dose of 200 CGy (n=30 survived the procedure, w hereas irradiation with 400 cGy (n=23) or 800 cGy (n=12) resulted in s ignificant mortality (78% and 100%, respectively). Engraftment was mon itored by determining ASB activities in peripheral white blood cells a nd by Y chromosome in situ hybridization analysis. Fifty-two percent o f the animals from the 200-cGy group engrafted for up to 8 months afte r BMT; among the five animals that survived the 400-cGy dose, all engr afted. In comparison, only 20% of nonirradiated animals engrafted at l ow levels. Of the 24 engrafted animals that were monitored for 8 month s after BMT, clinical and/or radiographic improvements were noted in o nly one (BMT animal 3). Enzymatic analysis revealed that the ASB activ ities in the reticuloendothelial organs of this animal, as well as two other engrafted but clinically unimproved animals (BMT animals 1 and 2), were normal or near normal; correspondingly, the glycosaminoglycan levels in these organs were significantly reduced. Consistent with th e clinical and biochemical observations, light and electron microscopi c findings were more im-proved in BMT animal 3 as compared with BMT an imals 1 and 2, although a reduction of storage was evident in each of these transplant recipients, particularly in the trachea and aorta, tw o tissues that are characteristic sites of pathology in human patients . Conclusions. These results indicate that EMT in newborn MPS VI patie nts may prevent many of the pathological and clinical findings in this disorder, but is likely to have very limited and unpredictable effect s on the skeletal abnormalities.