Lysosomal Storage Disorders: Gene Therapy


History, therapeutic alternatives and different approaches to gene transfer in lysosomal storage diseases are important for the understanding of this group of inborn errors of metabolism. Recent advances have proved that gene therapy will soon be a part of standard medical practice.

Keywords: gene therapy; Gaucher disease; mucopolysaccharidosis, neonatal gene transfer; hematopoietic stem cell gene transfer

Figure 1.

(a) Cells lacking the enzyme are engorged with nondegraded substrate and (b) are subjected to gene transfer using viral and/or nonviral vectors; (c) expression of the therapeutic gene results in the production of the therapeutic enzyme, which is either taken by the lysosome or is secreted; (d) catabolism of stored substrate occurs in the production of enzymatically corrected cells; (e) cell function is restored. AAV: adeno‐associated virus; LV: lentivirus; RV: retrovirus.

Figure 2.

(a) Normal degradation of complex molecules in the lysosome; (b) accumulation of catalytic products produced by transporter abnormalities; (c) treatment model for cystinosis. A carrier molecule transported by an alternative pathway is administered and binds to the accumulated molecules. Both molecules leave the lysosome by means of a normal transporter.

Figure 3.

(a) Normal enzymes with normal targeting signals are directed to the lysosomal compartment by receptor‐mediated endocytosis; (b) normal enzymes with abnormal targeting signals cannot enter the lysosomal compartment, hence the substrate accumulation.



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Cabrera‐Salazar, Mario A, and Barranger, John A(Jan 2006) Lysosomal Storage Disorders: Gene Therapy. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005754]