Gene for Lysosomal Storage Disease

Applied Genetics News, June, 2001

At American Society of Gene Therapy's annual meeting, Seng Cheng, vice president for genetic diseases science at Genzyme (One Kendall Square, Cambridge, MA 02139-1563; Tel: 617/252-7500, Fax: 617/374-7368, Website: www.genzyme.com), reviewed preclinical studies demonstrating the feasibility of gene therapy for Fabry disease, a lysosomal storage disorder that arises from the loss of the enzyme alpha-galactosidase. Genzyme has developed an enzyme replacement therapy for Fabry disease, Fabrazyme (agalsidase beta), which has received a positive opinion from the Committee for Proprietary Medicinal Products in Europe and is under review with the U.S. Food and Drug Administration.

Cheng and other Genzyme researchers have been able to demonstrate clearance of GL-3 lipid storage from affected tissues following gene transfer in preclinical studies of Fabry disease, an important "proof of concept" of the feasibility of using gene therapy to treat this disease. This result was achieved with both adenovirus and adeno-associated virus (AAV) vectors, and the effect persisted for 6 months. AAV vectors, which Genzyme is exploring in collaboration with Targeted Genetics, are particularly promising for treatment of lysosomal storage disorders such as Fabry disease, as they yield long-term expression and appear safer than current-generation adenovirus vectors for the treatment of chronic diseases. These results are likely to be applicable to other storage disorders and will form the basis for a common approach to treating these diseases.