Fabry disease is an X-linked monogenic disorder caused by mutations in galactosidase alpha (GLA) gene that encodes the enzyme α-galactosidase A (α-Gal A). α-Gal A metabolizes globotriaosylceramide substrate in lysosome. ST-920 is an adeno-associated virus encoding a human GLA cDNA under the control of a liver-specific promoter. Direct coat anti-α-Gal A antibody assays were developed to evaluate antibody response to the transgene enzyme expressed endogenously in non-human primates and humans. The bridging assay format was not feasible due to dimerization of the conjugated recombinant human α-Gal A reagents. This presentation highlights the challenges of developing a sensitive direct coat ELISA for non-clinical and clinical applications. In addition, the presentation demonstrates the innovative solutions to deliver reliable assays, which includes assessing well-characterized recombinant protein similar to the enzyme replacement therapy standard, engineering a chimeric anti-α-Gal A antibody positive control, and selecting detection antibody that cross-reacts with monkey and human IgG/IgM. .
The audience will understand the basic background about Fabry disease and information about ST-920 AAV mediate gene therapy for the disorder
The participants will understand the challenges associate with gene therapy and immunogenicity assay development
The audience will be shown innovative solutions to overcome immunogenicity assay development challenges to support non-clinical and clinical studies.