Active immunotherapy reduces NOTCH3 deposition in brain capillaries in a CADASIL mouse model.

ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of familial small vessel disease; no preventive or curative therapy is available. CADASIL is caused by mutations in the NOTCH3 gene, resulting in a mutated NOTCH3 receptor, with aggregation of the NOTCH3 extracellular domain (ECD) around vascular smooth muscle cells. In this study, we have developed a novel active immunization therapy specifically targeting CADASIL-like aggregated NOTCH3 ECD. Immunizing CADASIL TgN3R182C¹⁵⁰ mice with aggregates composed of CADASIL-R133C mutated and wild-type EGF_1-5 repeats for a total of 4 months resulted in a marked reduction (38-48%) in NOTCH3 deposition around brain capillaries, increased microglia

SUBMITTER: Oliveira DV 

PROVIDER: S-EPMC9906330 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature