Approach to gene therapy of glycogenosis type II (Pompe disease)

Pompe disease is a generalized lysosomal glycogenosis affecting essentially the skeletal muscles and the heart. It is due to the deficiency of acid cy -glucosidase, also called acid maltase, involved in glycogen degradation by the cleavage of alpha-1,4 and alpha-1,6 glycosidic linkages. The severe in fantile, milder juvenile, and late-onset or adult forms are associated unde r the generic name of glycogenoses type II. The clinical picture can differ according to these variants, forming a clinical spectrum from cardiorespir atory failure with early death in the infantile variant to late muscular we akness or respiratory problems in the adult variant. Enzymatic pre- and pos tnatal diagnoses and mutation characterization are available. Different the rapeutic attempts have been conceived and some of them have come to clinica l trials. Several pilot studies have demonstrated the feasibility of gene t herapy and remarkable advances have been realized. Of particular interest, strategies for gene therapy in at generalized disease like Pompe disease mu st be accompanied by the secretion and uptake of the corrective enzyme by m ore distant cells or tissues in order to obtain efficient results. Prelimin ary positive results have been obtained in animal models, and near approach es with improvements in the access to muscle and heart, in the efficacy and innocuity of vectors, and in the clinical evolution are proposed. Gene the rapy is a promising strategy for Pompe disease. However, several steps must be explored before this method becomes clinically successful. (C) 2000 Aca demic Press.