Metabolic defects, gene therapy

Lysosomal storage disorders (LSDs) constitute an important group of conditions in which the potential of gene manipulation as therapy can be assessed. They are monogenic defects, often with severe manifestations for which there are limited treatment options. Overexpression of tlie lysosomal hydrolase by gene-conected cells results in secretion of some of the enzyme and its uptake by uncorrected bystander cells (metabolic cooperativity). Gene therapy shategies, enzyme therapy and bone maiiow transplantation have all been described. 

Gene therapy for this metabolic defect may become available within the next few years. In vitro studies have demonstrated the feasibility of retroviral-mediated gene transfer of both the El-a and E2 subunits of the branched-chain decarboxylase complex [16,18],... 

Many diseases, such as hereditary metabolic defects and tumors, can still not be adequately treated. About 10 years ago, projects were therefore initiated that aimed to treat diseases of this type by transferring genes into the affected cells (gene therapy). The illustration combines conceivable and already implemented approaches to gene therapy for metabolic defects (left) and tumors (right). None of these procedures has yet become established in clinical practice. 

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