Why is this research needed?
Stroke can be caused by many different factors. There are some factors we can change to reduce our risk. Our genetics play a role in the likelihood of having a stroke, but we cannot change them.
CADASIL, which stands for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is one of the most common genetic causes of stroke and dementia.
The disease causes thickening of blood vessel walls which can block the flow of blood to the brain and cause damage, including strokes. The symptoms people with the disease experience and when they start vary widely, with signs typically appearing in people in their mid-30s. Some people may not show signs of the disease until later in life.
The disease is caused by mutations (error in our genetics) in a gene called NOTCH3. The gene controls muscle cells around blood vessels that affect blood flow.
Overall, the disease is rare but there is no treatment to help people with CADASIL reduce their risk of stroke and dementia.
What is this research aiming to do?
This work paves the way for new treatments for CADASIL that can stop stroke happening, and will allow us to better understand the ways that mutations cause disease.
How will they do this?
The researchers will create the CADASIL ‘disease-in-a-dish’ allowing them to study why people with the disease are at a higher risk of stroke and test new treatments to reduce the risk of stroke.
By taking a piece of skin donated by people with CADASIL, they will make human stem cells that can turn into any type of new cell. They will make muscle cells (called smooth muscle cells; SMC) from the stem cells. This way the SMCs will have the same abnormalities as people with CADASIL.
The researchers successfully made SMCs from skin donated by people with CADASIL.
They found differences between the SMCs in people with and without the disease. For example, SMCs with the mutation that cause CADASIL are more likely to die. There are also problems with how the brain cells worked together which may cause damage in the brain. This uncovers a possible new cause of stroke and dementia in people with CADASIL.
The researchers can continue to use the CADASIL ‘disease-in-a-dish’ to test whether new treatments can target these problems to reduce the risk of stroke.