Abstract

This project is looking at the effects of changes to the COL4 gene in different models, to understand exactly how they cause small vessel disease.
The team have developed a new animal model that has the increased risk version of COL4, so they can study the onset and progression of stroke and how changes in the scaffolding matrix affect the function of the neurovascular unit. Understanding what causes small vessel disease could help to identify new drug targets, and developing new models like these to test new drugs will speed up drug discovery. This will hopefully lead to new treatments which can either prevent or halt small vessel disease, which could delay the onset of some forms of vascular dementia.
Studying how the disease progresses in animal models could also help to identify biological signals such as particular molecular changes or differences in memory and thinking that can be used to recognise the disease. They are also looking at the effects of the gene in models of neurovascular unit cells, which they have developed from the stem cells of people with disease-related changes to COL4. Cellular models like these could be used to rapidly test new drugs for small vessel disease.
This programme is bringing together experts in animal and human models, and specialists in stroke. This will allow the researchers to relate what they see in models to what they see in people with the condition, which will help identify targets for treatments.