Table 1.
Comparison of discrepant amenability assay results from Benjamin et al. and Oommen et al.
| Variant | Benjamin et al [1] (GLP-HEK) data |
Oommen et al [2] data |
|||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline α-Gal A |
α-Gal A activity with 10 μM migalastat |
Mann-Whitney U P value (one-tail) | Absolute increase (% WT) | Relative increase (fold) | Relative increase by % WT activity | Amenable? (Yes/No) | Baseline α-Gal A |
α-Gal A activity with 10 μM migalastat |
Mann-Whitney U P value (one-tail) | Absolute increase (% WT) | Relative increase (fold) | Amenable? (Yes/No) | |||||
| (nmol/mg/h) | (% WT) | (nmol/mg/h) | (% WT) | (nmol/mg/h) | (% WT) | (nmol/mg/h) | (% WT) | ||||||||||
| A108T | 20,760 | 57.1 | 29,391 | 80.8 | 0.0002 | 23.7 | 1.42 | 1.41 | Yes | 14,287 | 73.3 | 16,476 | 84.5 | NA | 11.2 | 1.15 | No |
| S126G | 34,476 | 83.7 | 46,491 | 113.9 | 0.0001 | 30.2 | 1.35 | 1.36 | Yes | 36,722 | 143.7 | 43,598 | 170.6 | NA | 26.9 | 1.19 | No |
| D175E | 15,726 | 44.3 | 18,946 | 53.4 | 0.0206 | 9.1 | 1.20 | 1.21 | Yes | 23,110 | 57.9 | 26,931 | 67.4 | NA | 9.6 | 1.17 | No |
| S304 N | 30,563 | 94.1 | 39,629 | 121.8 | 0.0001 | 27.7 | 1.30 | 1.29 | Yes | 19,488 | 77.8 | 22,622 | 90.4 | NA | 12.5 | 1.16 | No |
| D264A | BLD | BLD | BLD | BLD | NA | NA | NA | NC | No | 1020 | 4.4 | 1840 | 7.9 | NA | 3.5 | 1.80 | Yes |
| S276G | BLD | BLD | 694 | 2.0 | 0.0001 | 2.0 | NC | NC | No | 1252 | 3.0 | 8764 | 21.0 | NA | 18.0 | 7.00 | Yes |
The amenability criteria for the GLP-HEK assay are ≥1.20-fold over baseline with an absolute increase of ≥3.0% wild-type α-Gal A activity in the presence of 10 μM migalastat.
α-Gal A = α-galactosidase A; BLD = below level of detection; GLP-HEK = good laboratory practice-validated HEK293 cell assay; NA = not applicable; NC = not calculated; WT = wild-type.