Cerebral small vessel disease (SVD), a condition in which the structure and function of the small vessels in the brain progressively become impaired, accounts for 20% of all ischaemic strokes. SVD is often clustered in families, and it is now known that a number of inherited abnormalities in the genome may underlie these familial forms of SVD. An example of this is CADASIL, where there has been an alteration in the gene known as NOTCH3.
Other rare inherited diseases have also been found to produce symptoms similar to those seen in CADASIL, such as migraines, strokes and cognitive impairment. However, the diagnostic tests for these diseases are expensive and not widely available. In addition, there are some families in whom these tests are negative, but are likely to have abnormalities in other genes that have yet to be discovered.
To address these challenges, the National Institute for Health Research, Cambridge University and Cambridge University Hospitals NHS Foundation Trust jointly funded a research project which involved researchers from across England, and was coordinated from the University of Cambridge. This project, known as the BRIDGE project, studied patients with CADASIL-like disease in whom CADASIL screening for the NOTCH3 gene mutation has been negative. This project aimed to uncover the genes underlying these rare causes of SVD, to develop new diagnostic techniques, and to support the development of targeted treatment strategies for these diseases. The BRIDGE study was selected as a pilot study for Genomics England (GeL) by the Department of Health.