Gene therapy: prospects for glycolipid storage diseases.
Lysosomal storage diseases comprise a group of about 40 disorders, which in most cases are due to the deficiency of a lysosomal enzyme. Since lysosomal enzymes are involved in the degradation of various compounds, the diseases can be further subdivided according to which pathway is affected. Thus, enzyme deficiencies in the degradation pathway of glycosaminoglycans cause mucopolysaccharidosis, and deficiencies affecting glycopeptides cause glycoproteinosis. In glycolipid storage diseases enzymes are deficient that are involved in the degradation of sphingolipids. Mouse models are available for most of these diseases, and some of these mouse models have been used to study the applicability of in vivo gene therapy. We review the rationale for gene therapy in lysosomal disorders and present data, in particular, about trials in an animal model of metachromatic leukodystrophy. The data of these trials are compared with those obtained with animal models of other lysosomal diseases.
Gieselmann
Volkmar
V
Institut für Physiologische Chemie, Rheinische-Friedrich-Wilhelms Universität, Bonn 53115, Germany. gieselmann@institut.physiochem.uni-bonn.de
Matzner
Ulrich
U
Klein
Diana
D
Mansson
Jan Eric
JE
D'Hooge
Rudi
R
DeDeyn
Peter D
PD
Lüllmann Rauch
Renate
R
Hartmann
Dieter
D
Harzer
Klaus
K
D000818:Animals; D015316:Genetic Therapy / Q000639:trends*; D006801:Humans; D013106:Sphingolipidoses / Q000628:therapy*