Engineering α-galactosidase A to Improve Protein Stability, Efficacy and Reduced Immune Response for Treatment of Fabry Disease
Abstract
Fabry disease is an X-linked genetic disorder arising from a deficiency in α-galactosidase A (GLA). Low levels of GLA activity result in the accumulation of globotriaosylceramide (Gb3, GL-3, ceramide trihexoside) in the lysosomes of a variety of tissues, including heart, kidney, liver, and blood vessels. For Fabry disease, enzyme replacement therapy (ERT) is available. However, issues that routinely compromise the efficacy of ERTs are short in vivo half-life, and the development of anti-drug antibodies. This limits the efficacy of treatment and may cause side-effects. Therefore, the development of ERTs with enhanced stability and reduced immunogenicity would be beneficial.
Find out how we engineered a-galactosidase A (GLA) for these properties as a potentially more effective treatment of Fabry disease.