In 2021, with donations from supporters like you, CADASIL Eradication Project began funding innovative efforts at UW Medicine to better understand the nature of CADASIL’s impact on those who have the disease. CADASIL is a genetic syndrome that leads to “small vessel disease” strokes. These are brain injury strokes due to dysfunction in the small vessels of the brain.
We don’t understand how the CADASIL gene causes the small vessels to no longer provide enough blood to the brain tissue it supplies. There are a number of different cell types that make up small vessels, so understanding how each of them contribute to the disease is critical to developing therapies. Further understanding how dysfunction of the blood vessels is then altering the other surrounding non-vessel cells like immune cells, neurons and supportive cells, can also reveal important biology and potential therapeutic targets.
Researchers at UW Medicine are creating complex 3-D models of human brain vessels made from individuals with and without CADASIL. With this new system we can not only capture the gene and protein changes caused by CADASIL, but also how CADASIL alters the function of 1) each cell and 2) the blood vessel as a whole – how the cells work together. Using these models we can measure blood flow dynamics, vessel integrity, and test factors that modulate blood vessel function.
These methods aim to uncover the biology regulating small blood vessels and neighboring brain tissue. This work is therefore important to small vessel diseases more broadly, a common cause of stroke in the U.S.