Christina Sjöstrand

CADASIL is the most common monogenic form of cerebral small vessel disease (SVD), a group of diseases affecting more than 5.000 individuals per year in Sweden. CADASIL is caused by mutations in the NOTCH3 gene and CADASIL patients experience arteriopathy and ischemic infarcts, ultimately leading to cognitive impairment and premature death. There are currently no therapies for CADASIL, and we will therefore explore two novel therapy strategies in a CADASIL mouse model: immunization and neuroinflammation/STING blockade. To monitor disease progression in CADASIL patients, better biomarkers are warranted. We will identify potential biomarkers from a large-scale transcriptomic dataset from a CADASIL mouse model, evaluate candidate biomarkers in human and mouse histological material and assess their efficacy in blood samples from CADASIL patients, with a particular focus on neuroinflammation. Finally,  non-CADASIL disease-causing NOTCH3 mutations are emerging, and we will search for such mutations in a small cohort of “atypical” SVD and migraine patients and establish how non-CADASIL NOTCH3 mutations affect Notch signalling. Information about non-CADASIL NOTCH3 mutations is important for future therapy considerations. In sum, through a multipronged approach spanning from preclinical transcriptomic and mouse model analysis to biomarker analysis in CADASIL patients, we expect to make progress beyond the state-of-the-art in CADASIL therapy and monitoring of disease progress.