Stopping the Stops in HHT
Research type
Research Study
Full title
Nonsense substitutions in hereditary haemorrhagic telangiectasia (HHT)
IRAS ID
211223
Contact name
Claire Shovlin
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
3 years, 11 months, 30 days
Research summary
Hereditary Haemorrhagic Telangiectasia (HHT) is an inherited condition that causes vascular malformations to form in the nose (leading to bleeds) and internal organs, such as the lungs, liver and brain. Currently there are few effective treatments for HHT.
On average, individuals with HHT pass on HHT to half of their children. This is because they have a mistake in their DNA that codes for signalling molecules in blood vessel cells. Gene changes (mutations) have been identified in three different genes, all of which disrupt the same signalling pathway that is important for blood vessels to develop properly. Our hypothesis is that if we can correct the abnormal cell signalling that results from these DNA changes, we may be able to reduce the amount of bleeding, improving survival and quality of life. A new group of molecular therapies provide a novel opportunity to actually correct the message from mutated HHT genes. In this study, we will take the first steps towards that goal, and test two different drugs using cells from patients with HHT.
These drugs work by enabling cells to bypass a particular type of DNA gene change known as a nonsense mutation. These mutations produce a “stop” signal that occurs too early in the message from the gene, and prevents the cell from making the correct protein. By “stopping the stops” and changing them back to “go”, these drugs should allow HHT cells to start making the correct protein again, at the right time, and in the right place. It is then not necessary to fully understand when the proteins need to be made- the drugs would allow the cell to decide. We will isolate blood cells to test whether either drug can correct the abnormal signalling. If successful, the next step will be to design clinical trials.
REC name
East of Scotland Research Ethics Service REC 2
REC reference
16/ES/0095
Date of REC Opinion
12 Aug 2016
REC opinion
Favourable Opinion