Reverse transcriptase inhibitors in Aicardi-Goutières syndrome: A crossover clinical trial

Abstract

Aicardi-Goutières syndrome (AGS) is a childhood disease particularly affecting the brain. There is a close link between AGS and increased amounts of a chemical called interferon. Interferon is normally only produced following viral infection. In AGS there is no viral infection. Rather, an affected individual's cells are confused into thinking that their own genetic material comes from a virus, so that they produce interferon continuously. This interferon acts as a poison that damages cells. An obvious way then to treat AGS would be to reduce interferon production.

In 2018, a clinical trial was published involving the use of drugs called reverse transcriptase inhibitors (RTIs) in AGS. It was predicted that RTIs might block the production of ‘self-derived’ genetic material that was triggering interferon production in patients with AGS. Using these RTIs, interferon levels fell, and then increased again when the drugs were stopped. Based on these findings a new trial was designed using these same drugs given individually and in combination, again monitoring their effect on interferon levels. This trial, funded by the Medical Research Council, involved doctors in Edinburgh, Birmingham, Manchester, and London, and was open to patients under 16 years of age with specified genetic forms of AGS.