Syngeneic bone marrow transplantation reduces the hearing loss associated with murine mucopolysaccharidosis type VII.
نویسندگان
چکیده
MPS VII mice are deficient in beta-glucuronidase and share many clinical, biochemical, and pathologic characteristics with human mucopolysaccharidosis type VII (MPS VII). We have shown that syngeneic bone marrow transplantation (BMT) prolongs survival and reduces lysosomal storage 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 development of deafness and the associated pathology in the MPS VII mouse. Eleven weeks after syngeneic BMT performed at birth, treated MPS VII mice had normal auditory-evoked brainstem responses (ABR), whereas untreated MPS VII mice had ABR thresholds 43 dB higher than normal. Treated MPS VII mice had beta-glucuronidase-positive cells in the temporal bone and in the subepithelial connective tissue of the external auditory canal. There was less thickening of the tympanic membrane and middle ear mucosa and decreased distortion of the ossicles and the cochlear bone. 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 than untreated mutants. These data indicate that syngeneic BMT in newborn MPS VII mice prevents early hearing loss and, in some animals, results in long-term improved auditory function.
منابع مشابه
Syngeneic Bone Marrow Transplantation Reduces the Hearing Loss Associated With Murine Mucopolysaccharidosis Type
MPS VI1 mice are deficient in P-glucuronidase and share many clinical, biochemical, and pathologic characteristics with human mucopolysaccharidosis type VI1 (MPS VII). We have shown that syngeneic bone marrow transplantation (BMT) prolongs survival and reduces lysosomal storage in many organs of the MPS VI1 mouse. In this report, we quantify the hearing loss and determine the impact of syngenei...
متن کاملMurine mucopolysaccharidosis type VII: long term therapeutic effects of enzyme replacement and enzyme replacement followed by bone marrow transplantation.
We demonstrated previously that short term administration of recombinant beta-glucuronidase to newborn mice with mucopolysaccharidosis type VII reduced lysosomal storage in many tissues. Lysosomal storage accumulated gradually after cessation of enzyme replacement therapy. Mice alive at 1 yr of age had decreased bone deformities and less lysosomal storage in cortical neurons. Here we compare th...
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Bone marrow transplantation (BMT) is relatively effective for the treatment of lysosomal storage diseases. To better understand the contribution of specific hematopoietic lineages to the efficacy of BMT, we transplanted b-glucuronidase–positive mononuclear phagocytes derived from either the peritoneum or from bone marrow in vitro into syngeneic recipients with mucopolysaccharidosis type VII (MP...
متن کاملBehavior and therapeutic efficacy of beta-glucuronidase-positive mononuclear phagocytes in a murine model of mucopolysaccharidosis type VII.
Bone marrow transplantation (BMT) is relatively effective for the treatment of lysosomal storage diseases. To better understand the contribution of specific hematopoietic lineages to the efficacy of BMT, we transplanted beta-glucuronidase-positive mononuclear phagocytes derived from either the peritoneum or from bone marrow in vitro into syngeneic recipients with mucopolysaccharidosis type VII ...
متن کاملMurine Mucopolysaccharidosis Type
We have characterized a new mutant mouse that has virtually no /-glucuronidase activity. This biochemical defect causes a murine lysosomal storage disease that has many interesting similarities to human mucopolysaccharidosis type VII (MPS VII; Sly syndrome; fl-glucuronidase deficiency). Genetic analysis showed that the mutation is inherited as an autosomal recessive that maps to the fl-glucuron...
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ورودعنوان ژورنال:
- Blood
دوره 86 5 شماره
صفحات -
تاریخ انتشار 1995