Identifying Mutant Forms of α-Galactosidase A for Fabry Disease Treatment
Author Information
Author(s): Wu Xiaoyang, Katz Evan, Valle Maria Cecilia Della, Mascioli Kirsten, Flanagan John J, Castelli Jeffrey P, Schiffmann Raphael, Boudes Pol, Lockhart David J, Valenzano Kenneth J, Benjamin Elfrida R
Primary Institution: Amicus Therapeutics
Hypothesis
Can a cell-based assay identify mutant forms of α-Galactosidase A that respond to the pharmacological chaperone AT1001?
Conclusion
The HEK-293 cell-based assay can effectively identify mutant forms of α-Gal A that are likely to respond to AT1001 in vivo.
Supporting Evidence
- 49 out of 81 mutant forms showed a significant increase in α-Gal A activity in response to AT1001.
- The assay results were consistent with responses observed in patient-derived lymphoblasts.
- Responses to AT1001 were correlated with baseline α-Gal A activity.
- Clinical studies indicated that the HEK-293 cell-based assay can identify patients likely to respond to treatment.
Takeaway
Scientists created a test to find out which versions of a protein called α-Gal A can be helped by a medicine called AT1001, which is used to treat a disease called Fabry disease.
Methodology
A cell-based assay in HEK-293 cells was developed to test the response of 81 mutant forms of α-Gal A to AT1001.
Potential Biases
Potential bias in the selection of mutant forms and patient demographics.
Limitations
The study primarily focused on male patients, and results may not be generalizable to female patients with mosaic expression of α-Gal A.
Participant Demographics
Male Fabry patients with various mutations in the α-Gal A gene.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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