The Effects of IRL-1620 in Post-ischemic Brain Injury: A Systematic Review and Meta-analysis of Experimental Studies.

Abstract

Sovateltide (IRL-1620), an endothelin B receptor agonist, has previously demonstrated neuroprotective and neuroregenerative effects in animal models of acute ischemic stroke. Recently, clinical trials indicated that it could also be effective in humans with stroke. Here, we systematically investigate whether IRL-1620 may be used for the treatment of ischemia-induced brain injury. A systematic review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. MEDLINE (PubMed) and Scopus databases were searched for eligible studies up to December 2022. The databases ClinicalTrials.gov and Pharmazz Inc. were screened for unpublished or ongoing trials. Only studies in English were evaluated for eligibility. Meta-analysis of the included studies was also conducted. Finally, seven studies were included in the review, all in animal rat models because of scarcity of clinical trials. Six studies, all in middle cerebral artery occlusion (MCAO) models, were selected for meta-analysis. In the two studies assessing mortality, no deaths were reported in the IRL-1620 group 24h after MCAO, whereas the vehicle group had almost a five times higher mortality risk (risk ratio 5.3, 95% confidence interval 0.7-40.1, I2 = 0%). In all five studies evaluating outcome on day 7 after MCAO, IRL-1620 was associated with statistically significantly lower neurological deficit and improved motor performance compared with the vehicle. Infract volume, differentiation potential of neuronal progenitor cells, and mitochondrial fate also improved with IRL-1620 administration. According to the above, in animal MCAO models, IRL-1620 enhanced neurogenesis and neuroprotection and improved outcome. Future studies are needed to expand our understanding of its effects in human study participants with acute ischemic stroke as well as in other common causes of cerebral ischemia including cardiac arrest.