TABLE 1.
overview of the parameters measured and comparison between PXL065 and pioglitazone effects. Green identifies similar results between PXL065 and pioglitazone, orange identifies different results
| Parameter | Model | Effect of PXL065 | Effect of pioglitazone | ||
|---|---|---|---|---|---|
| In vitro | VLCFA | ALD cell lines | AMN fibroblasts | Decrease in C26:0 and C24:0 | Decrease in C26:0 and C24:0 |
| C‐ALD fibroblasts | Decrease in C26:0 | Decrease in C26:0 | |||
| AMN lymphocytes | Decrease in C26:0 and C24:0 | Decrease in C26:0 and C24:0 | |||
| C‐ALD lymphocytes | Decrease in C26:0 and C24:0 | Decrease in C26:0 and C24:0 | |||
| Abcd1 null mice glial cells | Decrease in C26:0 | Decrease in C26:0 | |||
| Bioenergetics | ALD cell lines | AMN fibroblasts | Increase in basal and ATP‐linked OCR | No effect | |
| C‐ALD fibroblasts | Increase in basal and ATP‐linked OCR | Increase in basal OCR only | |||
| C‐ALD lymphocytes | Increase in basal, ATP‐linked and maximal OCR | Decrease in ATP linked OCR | |||
| Abcd1 null mice glial cells | Increase in basal, ATP‐linked and maximal OCR | No effect | |||
| ABCD2 – ABCD3 transporters | ALD cell lines | AMN fibroblasts | Increase in ABCD2 and ABCD3 expression | Increase in ABCD2 and ABCD3 expression | |
| C‐ALD fibroblasts | Increase in ABCD2 and ABCD3 expression | Increase in ABCD2 expression only | |||
| AMN lymphocytes | Increase in ABCD2 and ABCD3 expression | Increase in ABCD2 and ABCD3 expression | |||
| C‐ALD lymphocytes | No effect | No effect | |||
| Abcd1 null mice glial cells | Increase in ABCD2 and ABCD3 expression | No effect | |||
| Inflammation markers | C‐ALD lymphocytes | Decrease in gene expression in multiple inflammatory markers | Decrease in gene expression in multiple inflammatory markers | ||
| Stimulated Abcd1 null mice glial cells | Decrease in gene expression in multiple inflammatory markers | Decrease in gene expression in multiple inflammatory markers | |||
| In vivo | VLCFA | 6‐8‐week‐old Abcd1‐null mice | Decrease in C26:0 in plasma, brain, and spinal cord | Decrease in C26:0 in plasma and brain | |
| 13‐month‐old Abcd1‐null mice | Decrease in C26:0 in spinal cord | No effect | |||
| Open field test | 13‐month‐old Abcd1‐null mice | Decrease in total distance and total freezing time | No effect | ||
| Sciatic nerve axon morphology | 13‐month‐old Abcd1‐null mice | Decrease in stellate cell shape percentage | Decrease in stellate cell shape percentage | ||
Abbreviations: ALD, adrenoleukodystrophy; AMN, adrenomyeloneuropathy; C‐ALD, cerebral‐ALD; OCR, oxygen consumption rate; VLCFA, very long chain fatty acids.