Gene therapy in lysosomal diseases

Lysosomal storage diseases are monogenic metabolic disorders resulting from a deficiency in intralysosomal enzymes involved in macromolecule catabolis m. Various groups have been delineated according to the affected pathway an d the accumulated substrate: mucopolysaccharidoses, lipidoses, glycoprotein oses and glycogenosis type II. Their clinical severity and the absence of e fficient therapy for the majority of these disorders justify the developmen t of gene transfer methods. Most of the genes encoding the normal lysosomal enzymes have been cloned and recently numerous animal models have been obt ained for nearly alt these diseases. Due to the clinical heterogeneity of l ysosomal diseases, showing multivisceral Involvement or affecting predomina ntly the reticuloendothelial system, muscle or central nervous system, vari ous 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. (C) 2000 Editions scientifiqu es et medicales Elsevier SAS.