Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

Mucopolysaccharidosis type VII (MPS VII) is caused by a deficiency of the lysosomal enzyme beta-glucuronidase. Clinical manifestations include intralysosomal accumulation of undegraded glycosoaminoglycans. Various gene therapy approaches for the treatment of MPS VII have been described. We propose an alternative strategy, by implanting allogeneic cells enclosed in biocompatible and perm-selective microcapsules that allow the diffusion of nutrients, waste and therapeutic products, while excluding immune mediators. Since the cells are immuno-protected, the capsules may then be implanted into different patients requiring the same gene product, making this a cost-effective therapeutic approach. Fibroblasts expressing mouse beta-glucuronidase enclosed in microcapsules were implanted into MPS VII mice. Beta-glucuronidase activity was detected in the plasma, in the kidney for up to 4 weeks and in the liver and spleen for up to 8 weeks. Tissue sections showed a dramatic reduction in lysosomal storage lesions in the spleen and pathology reversal of the liver for up to 8 weeks. However, implanted mutant mice developed antibodies against the recombinant beta-glucuronidase, preventing long-term delivery in vivo, evidencing the difficulties to deliver therapeutic products to individuals with a null mutation. Recently, we have explored methods for delivery of beta-glucuronidase directly into the CNS for treatment lysosomal storage disease neurodegeneration.

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Poster Number PAross0669
Keywords: gene therapy, genetic disease, lysosome, encapsulation, microcapsules