ANIMAL MODELS OF MUCOPOLYSACCHARIDOSES

University Of Pennsylvania, Philadelphia PA

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Abstract

DESCRIPTION: This is a renewal application for the use of cat and rat models of human mucopolysaccaridoses for the development of approaches to therapy. Two disorders are presented: MPS I due to alpha-iduronidase (ID) deficiency, for which there is a cat model, and MPS VI due to aryl sulfatase B (ASB) deficiency for which there are cat and rat models. The specific aims are to (1) investigate pathogenesis, in particular as it applies to collagen synthesis on skeletal and ocular abnormalities, abnormal storage in neural cells, and the cell types catabolizing dermatan sulfate; (2) evaluate enzyme replacement and bone marrow transplantation as therapeutic strategies in both disorders; and (3) evaluate gene therapy approaches for MPS I and VI, including continuation of studies using progenitor cell implants in MPS VI cats, development of methods for fluorescence-based enrichment of of transduced bone marrow progenitors, development of novel vectors and procedure systems, and development of organ specific gene transfer technology.