Interferon signalling as a potentional therapeutic target in amyotrophic lateral sclerosis and frontotemporal dementia – protocol for a systematic review and meta-analysis v1

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no cure and limited treatment options. There is therefore an urgent need for effective therapeutic interventions in this disease. This protocol outlines the strategy for a systematic review and meta-analysis to identify, from in vivo animal studies, potential therapeutic interventions for ALS cases in which an interferon response is induced. Our aim is to perform a comprehensive review of the ALS literature to compile a list of (i) interventions affecting interferon signalling pathways and (ii) specific interferon signalling pathway targets that may be manipulated for therapeutic benefit in patients with ALS. We will do this by assessing the pre-clinical literature for the effects of interferon signalling pathway manipulation on the following primary and secondary outcome measures comparing models of ALS/FTD to controls; the primary outcome measure being survival, and secondary outcome measures including histological, biochemical, and behavioural metrics. We will also carry out a structured quality assessment of the literature to provide recommendations for future studies.