Gene therapy for mucopolysaccharidosis

Abstract

Mucopolysaccharidoses (MPS) are due to deficiencies in activities of lysosomal enzymes that degrade glycosaminoglycans. Some attempts at gene therapy for MPS in animal models have involved intravenous injection of vectors derived from an adeno-associated virus (AAV), adenovirus, retrovirus or a plasmid, which primarily results in expression in liver and secretion of the relevant enzyme into blood. Most vectors can correct disease in liver and spleen, although correction in other organs including the brain requires high enzyme activity in the blood. Alternative approaches are to transduce hematopoietic stem cells, or to inject a vector locally into difficult-to-reach sites such as the brain. Gene therapy holds great promise for providing a long-lasting therapeutic effect for MPS if safety issues can be resolved.

Keywords::

• gene therapy
• glycosaminoglycan
• lysosomal storage disease
• mucopolysaccharidosis

Acknowledgements

The authors thank M Sands for helpful suggestions on the manuscript. This work was supported by DK066448 awarded to KP Ponder and RR02512, DK25759, DK54481 awarded to ME Haskins.

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