Targeting VEGF-mediated blood-brain barrier disruption in advanced cerebral leukodystrophy.
J Neuroimmunol
; 393: 578395, 2024 Jun 13.
Article
em En
| MEDLINE
| ID: mdl-38897089
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Neuroimmunol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos