AGS-RTI (Aicardi-Goutières Syndrome-Reverse Transcriptase Inhibitors)
Research type
Research Study
Full title
Inhibition of reverse transcription in type I interferon mediated neuropathology
IRAS ID
280253
Contact name
Yanick Crow
Contact email
Sponsor organisation
University of Edinburgh
Eudract number
2020-003502-31
Duration of Study in the UK
2 years, 3 months, 31 days
Research summary
Aicardi-Goutières syndrome (AGS) is a disease of children, particularly affecting the brain and the skin. There is a close link between AGS and increased amounts of a chemical called interferon. Normally, we only produce interferon when we are infected with a virus. In AGS, there is no viral infection. Instead, the cells in the cells of affected patients are confused into thinking that their own genetic material is coming from a virus. As a result they produce interferon all the time, which acts as a poison that damages the cells.
A large amount of our own DNA is made up of ancient virus called ‘endogenous retrovirus’. These endogenous retroviruses can still act like a virus coming from outside of the body, so that they need to be controlled. We have wondered if the genetic changes causing AGS mean that these normal control mechanisms don’t work, so that the endogenous retroviruses start to make copies of themselves, which are then recognised by our immune system as ‘foreign’, leading to the continuous production of interferon.
We wish to treat AGS patients with drugs called reverse transcriptase inhibitors (RTIs), used to fight the HIV-1 virus that causes AIDS. In a recent study, we gathered early information suggesting that this treatment reduced interferon levels in patients with AGS, with levels increasing again when we stopped the drugs. Our new trial involves the use of the same drugs, but this time given individually and in combination. We will monitor the effect of treatment on interferon levels, and look at other markers which might give us clues to how the drugs are working. The trial is funded by the Medical Research Council, and involves experts based in Edinburgh, Birmingham, Manchester and Great Ormond Street Hospital.
REC name
London - Brent Research Ethics Committee
REC reference
20/LO/1150
Date of REC Opinion
4 Dec 2020
REC opinion
Further Information Favourable Opinion