London: Researchers supported by Cambridge Biomedical Research Centre (CBRC) have grown small blood vessel-like models in the lab and used them to show how damage can cause them to leak, leading to conditions such as vascular dementia and stroke.
Cerebral small vessel disease (SVD) is a leading cause of age-related cognitive decline and contributes to almost half of dementia cases worldwide. It is also responsible for one in five of ischemic strokes where a blood clot prevents the flow of blood and oxygen to the brain.
There are two main types of cerebral SVD. The most common is linked to high blood pressure and type 2 diabetes. The rare type is usually caused by a mutation in a gene called COL4.
The researchers took skin cells from people with the rare form of SVD. They used these to create stem cells. Using these stem cells the researchers created a model of the disease found in the brain vessels. The mutation causes disruption in structures and the blood vessels become leaky.
They found disruption is linked to overproduction of molecules called matrix metalloproteinases (MMPs). The team treated the cells with two drugs that inhibit MMPs: antibiotic doxycycline; anti-cancer drug marimastat.
The researchers found that inhibiting the MMPs stopped the leaking. But, they noted that these drugs can have serious side effects.
Commenting on the research, Dr Alessandra Granata, Department of Clinical Neurosciences at Cambridge, who led the study, said,“Despite the number of people affected worldwide by small vessel disease, we have little in the way of treatments because we don’t fully understand what damages the blood vessels and causes the disease. Most of what we know about the underlying causes tends to come from animal studies, but they are limited in what they can tell us. That’s why we turned to stem cells to generate cells of the brain blood vessels and create a disease model ‘in a dish’ that mimics what we see in patients.” “These particular drugs come with potentially significant side effects so wouldn’t in themselves be viable to treat small vessel disease. But they show that in theory, targeting MMPs could stop the disease. Our model could be scaled up relatively easily to test the viability of future potential drugs.”