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.