Could drugs that target faulty collagen treat brain haemorrhage?

Targeting intracellular pathways to dissect mechanisms of cerebrovascular disease

Dr Tom Van Agtmael and his team at the University of Glasgow are studying how blood vessel diseases lead to haemorrhage, or bleeding, in the brain. Around 15 percent of strokes involve a brain bleed and they can be fatal, so we need to find ways to prevent them. Cells in blood vessel walls are surrounded by a matrix of proteins that provide structure and strength to the vessels. Dr Van Agtmael has found that some people with inherited faults in one of these matrix proteins, collagen IV, are prone to brain haemorrhage. He has shown that the faulty collagen protein builds up inside cells, stressing the cells and leading to blood vessel disease. Mice with the abnormal collagen IV protein also develop bleeding in the brain. Dr Van Agtmael and his team have identified compounds that could improve the brain bleeding by reducing mutant collagen accumulation in cells. In this project, he will test these compounds in mice to see if and how they work. The researchers will use samples from patients with faulty collagen genes to see if these compounds could also work in humans. This research will tell us how faulty collagen IV causes brain bleeds, and if targeting collagen accumulation could treat people with inherited collagen IV mutations. Recently, studies have found that variations in collagen genes are associated with brain haemorrhage in the general population, meaning results from this research could be relevant to many more stroke patients. The compounds Dr Van Agtmael is testing are already approved for use in other diseases, so if they work here, they could benefit patients relatively quickly.