Gene therapy in lysosomal diseases

Lysosomal storage diseases are monogenic metabolic disorders resulting from a deficiency in intralysosomal enzymes involved in macromolecule catabolism. Various groups have been delineated according to the affected pathway and the accumulated substrate: mucopolysaccharidoses, lipidoses, glycoproteinoses and glycogenosis type II. Their clinical severity and the absence of efficient therapy for the majority of these disorders justify the development of gene transfer methods. Most of the genes encoding the normal lysosomal enzymes have been cloned and recently numerous animal models have been obtained for nearly all these diseases. Due to the clinical heterogeneity of lysosomal diseases, showing multivisceral involvement or affecting predominantly the reticuloendothelial system, muscle or central nervous system, various gene therapy strategies have to be developed. Vectors, ways of access, results and limits will be reviewed. Interesting results have already been obtained in the gene transfer for lysosomal diseases, but improvements are needed before a future application to humans.