CADASIL is a vascular protein aggregation disorder that is caused by NOTCH3 variants and causes adult stroke and dementia. A characteristic of CADASIL is the presence of NOTCH3 protein-containing Granular Osmiophilic Material (GOM) deposits in the basement membrane of small arteries.
Together with Gido Gravesteijn and his colleges from the Department of Clinical Genetics we subsequently investigated small arteries in the skin of CADASIL patients in which naturally occurring NOTCH3 exon skipping takes place and found that exon skipping diminishes NOTCH3 protein aggregation and disease severity. These results justify further therapeutic development of NOTCH3 correction for CADASIL!
Gravesteijn G, Munting LP, Overzier M, et al. Progression and Classification of Granular Osmiophilic Material (GOM) Deposits in Functionally Characterized Human NOTCH3 Transgenic Mice [published online ahead of print, 2019 Oct 30]. Transl Stroke Res. 2019;10.1007/s12975-019-00742-7. doi:10.1007/s12975-019-00742-7