This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mucopolysaccharidosis type IT (MPSTI), also known as Hunter syndrome is a lethal lysosomal storage disorder characterized clinically by coarse facial features, skeletal deformities with short stature, joint contractures, hepatosplenomegaly, and cardiopulmonary deterioration. In severe cases, children experience profound mental retardation and die before the age of 15. Current treatments are limited to bone marrow transplantation (BMT) and enzyme replacement therapy (ERT) which is still under investigation. Both therapeutic approaches have disadvantages and therefore, alternative strategies need to be investigated. Very encouraging results using vector derived from the Adeno-Associated virus (AAV) have been recently generated in the mouse model for this disease. We propose to further investigate safety and efficacy of AAV vectors for gene therapy of MPSII in a more clinically relevant animal model such as nonhuman primates. Nonhuman primates, like humans, are a natural host for AAV and they offer a unique opportunity for evaluating the safety and efficiency of gene-transfer with AAV vectors. In addition, nonhuman primates have a considerably longer lifespan than the commonly used laboratory animals, and therefore they are extremely important for assessment of long-term safety and gene expression following AAV-mediated gene transfer. These studies have the potential to generate preclinical data which will be immediately applicable for the treatment of this severe disease as well as other lysosomal disorders.
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