Abstract：
The earliest clinical manifestation of cerebral adrenoleukodystrophy (CALD) is adrenal insufficiency (AI) characterized by elevations in ACTH and loss of cortisol. We showed high (though physiologically achievable) levels of ACTH increases endothelial permeability, increases anisotropy, and increases VEGF secretion. An ACBD1 knockout endothelial cell line had increased sensitivity to ACTH and VEGF. Inhibition of VEGF via application of anti-VEGF (bevacizumab) improved permeability. Six boys with advanced CALD were treated with bevacizumab combined with dexamethasone and ruxolitinib as immune suppressants. Most boys had decreases in gadolinium enhancement on MRI indicating improvement in endothelial function, though all boys continued to progress symptomatically.
摘要：
脑肾上腺脑白质营养不良（CALD）的最早临床表现是肾上腺功能不全（AI），其特征是ACTH升高和皮质醇丢失。我们显示高水平的ACTH（尽管生理上可实现）增加内皮通透性，增加各向异性，并增加VEGF分泌。ACBD1敲除的内皮细胞对ACTH和VEGF的敏感性增加。通过应用抗VEGF(贝伐单抗)抑制VEGF改善了通透性。6名患有晚期CALD的男孩接受了贝伐单抗联合地塞米松和鲁索替尼作为免疫抑制剂的治疗。大多数男孩在MRI上的钆增强减少，表明内皮功能改善，尽管所有男孩都在积极地进步。
