Fabry Disease: Gene Therapy as an Emerging Alternative to ERT

The lysosomal storage disorder, Fabry disease is commonly treated with enzyme replacement therapy (ERT). ERT provides patients with recombinant forms of human α-galactosidase A, the enzyme which has reduced levels of activity in Fabry patients. Literature shows that patients who follow a regular regime of ERT experience a reduction in globotriaosylceramide (Gb3) accumulation and a decreased risk of renal, cardiac and cerebrovascular complications. Despite these clinical results, the high and recurring cost of ERT and its debatable long-term effectiveness suggest the need for alternative methods of treatment. This review will compare ERT with an emerging method of treatment: gene therapy. Gene therapy has been suggested for treating Fabry disease, in an attempt to normalize α-galactosidase A expression in targeted cells, thereby producing functional protein. Essentially, a functional α-galactosidase A gene is transduced into haematopoietic stem cells using a modified viral vector. Gene therapy may provide patients with a more convenient, less costly and long-term method of treatment. Recent developments of gene therapy pertaining to Fabry disease will be examined along with several issues that remain unresolved including the associated risks of insertional mutagenesis and the need for larger animal models.