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 are jointly funding a research project which involves researchers from across England, and will be coordinated from the University of Cambridge. This project, known as the BRIDGE project, will study patients with CADASIL-like disease in whom CADASIL screening for the NOTCH3 gene mutation has been negative. This project aims 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.
Genomics England Pilot Study
Genomics England (GeL) was established in 2013 by the Department of Health, with the aims of advancing the delivery of personalised treatment as part of the NHS, and to support scientific discovery and enable new medical insights. GeL’s flagship project is to sequence the genomes of 100 000 individuals by 2017. As the BRIDGE study has been selected as a pilot study for GeL, participants of BRIDGE may also be a part of the 100 000 Genomes Project. Participants who are suspected to have a genetic form of SVD, but do not fulfil the criteria for BRIDGE, may still be eligible to participate in GeL.
How to participate
The BRIDGE study is currently recruiting participants at the following sites, with a view to opening additional recruitment sites in the near future:
We are looking to recruit individuals who are suspected to have a familial form of small vessel disease, and have tested negative for known genetic causes of SVD, such as for abnormalities in the NOTCH3 gene which causes CADASIL. Both affected and unaffected family members of these individuals are also welcome to participate.