Gene therapy: prospects for glycolipid storage diseases
Gieselmann, Volkmar × Matzner, Ulrich Klein, Diana Mansson, Jan Eric D'Hooge, Rudi DeDeyn, Peter D Lüllmann Rauch, Renate Hartmann, Dieter Harzer, Klaus #
Philosophical transactions of the Royal Society of London. Series B, Biological sciences. vol:358 issue:1433 pages:921-925
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.