Systematic evidence-based approach to identifying and tailoring inflammation modulating treatments for patients with intracerebral haemorrhage

Background:

~40% patients die in the first month after intracerebral haemorrhage (ICH) and survival has not improved for >25 years.  The lack of treatments is partly due to incomplete understanding of causal mechanisms and the lengthy timelines and costs associated with drug development. While an expanding amount of research data are available to provide mechanistic insights, conventional evidence synthesis methods cannot handle their volume/complexity thus limiting their application.

Drug repurposing can accelerate the identification of effective treatments. The availability of safety data reduces drug development time and costs compared to de novo drug development. We developed systematic evidence-based approaches to guide drug repurposing in clinical trials of multiple sclerosis and MND.¹ While keeping up with exponentially increasing publication rates is challenging, advances in automation and artificial intelligence (AI) techniques make it feasible² and applying these techniques enables harnessing of data from different sources.  Systematic Online Living Evidence Summaries (SOLES)³ is a novel approach in evidence synthesis,  incorporating automation and AI to continuously gather, synthesise, summarise and report all evidence from a research domain, to inform drug repurposing.

Neuroinflammation occurs after ICH and is a therapeutic target. We have shown that interleukin-1β and neutrophils are abundant in ICH cases⁴ and that the inflammatory pathways involved vary according to the time after ICH onset (see page 8-9). Drugs which modulate the inflammatory response may improve outcome after ICH.

This PhD will develop a framework to identify, evaluate, and prioritise repurposed inflammation-modulating drugs in ICH. We will match information on potential candidate drugs with clinical features, aiming to tailor drug selection to a given patient.