SYNGENEIC BONE-MARROW TRANSPLANTATION REDUCES THE HEARING-LOSS ASSOCIATED WITH MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII

MPS VII mice are deficient in beta-glucuronidase and share many clinic al, biochemical, and pathologic characteristics with human mucopolysac charidosis type VII (MPS VII). We have shown that syngeneic bone marro w transplantation (BMT) prolongs survival and reduces lysosomal storag e in many organs of the MPS VII mouse. In this report, we quantify the hearing loss and determine the impact of syngeneic BMT on the develop ment of deafness and the associated pathology in the MPS VII mouse, El even weeks after syngeneic BMT performed at birth, treated MPS VII mic e had normal auditory-evoked brainstem responses (ABR), whereas untrea ted MPS VII mice had ABR thresholds 43 dB higher than normal. Treated MPS VII mice had beta-glucuronidase-positive cells in the temporal bon e and in the subepithelial connective tissue of the external auditory canal. There was less thickening of the tympanic membrane and middle e ar mucosa and decreased distortion of the ossicles and the cochlear bo ne. Although transplanted MPS VII mice had increased ABR thresholds by 33 weeks of age, four of the six had thresholds 12 to 32 dB lower tha n untreated mutants. These data indicate that syngeneic BMT in newborn MPS VII mice prevents early hearing loss and, in some animals, result s in long-term improved auditory function. (C) 1995 by The American So ciety of Hematology.