Fabry disease is one of about 40 lysosomal storage disorders that collectively affect approximately one in 7,700 people. Due to genetic defects, Fabry patients have a buildup of lipids (fats) in endothelial cells lining vessel walls, causing constriction. Eventually, cardiac disease, kidney disease or strokes result.
"Patients with Fabry disease either don't make enough of the enzyme alpha-galactosidase A or improper synthesis means the enzyme isn't active enough," says Jeffrey Medin, a U of T associate professor in the Department of Medical Biophysics and a scientist with the Ontario Cancer Institute at the Princess Margaret Hospital, one of three teaching hospitals of the University Health Network.
In research published in the Nov. 15 edition of the Proceedings of the National Academy of Sciences of the U.S.A., Medin and his colleagues demonstrated that an engineered lentiviral vector a type of retrovirus administered a day or two after birth can correct the defect long term in Fabry mice, ensuring they produce the appropriate enzyme at relevant levels. Further testing will be required before the therapy can be tried in humans.
"Our previous strategies targeted genetic correction of the disease in adult animals, and hence, older patients, but a lot of times the organ problems in Fabry disease are already initiated by the time the projected treatment started," says Medin. "A lot of Fabry patients also develop antibodies to the corrective gene product, so we decided we needed to come up with a better way to get around the immunity issue and administer treatment before the severe organ consequences became irreparable."
A therapeutic vector was employed to deliver the corrective gene. Throughout a
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15-Nov-2004