CADASIL is one of the most common genetic causes of stroke and dementia. This disease is caused by mutations (errors in the DNA) in the gene NOTCH3, which is found in the muscle layer of blood vessels in the brain. Currently there is no treatment for CADASIL because we don’t know how mutations in NOTCH3 cause disease.
In this study, human stem cells will be generated from a piece of skin donated by patients with CADASIL. From these stem cells, smooth muscle cells (SMCs) will be generated in a tissue culture dish in the lab. Both the human stem cells and SMCs will have the same abnormalities as the patient’s own blood vessel cells. This process effectively creates a ‘disease-in-a-dish’, which is a new human platform to study CADASIL, and which can be used to test new treatments.
This human platform will be used to understand the ways that mutations in NOTCH3 result in disease, with the aim of finding new targets that may be treated with drugs. Additionally, it will be used to test two new treatment strategies that directly target the cause of the disease; the mutated NOTCH3 protein.
This work may pave the way for new treatments for CADASIL, and will allow us to better understand the ways that mutations in NOTCH3 cause disease.