ApolipoproteinE mimetic peptides improve outcome after focal ischemia

Growing clinical evidence implicates isoform-specific effects of apolipoprotein E (apoE) in reducing neuroinflammation and mediating adaptive responses following ischemic and traumatic brain injury. However, the intact apoE holoprotein does not cross the blood–brain barrier and thus has limited therapeutic potential. We have created a small peptide, COG1410 (acetyl-AS-Aib-LRKL-Aib-KRLL-amide), derived from the apoE receptor-binding region. COG1410 retains the anti-inflammatory and neuroprotective biological properties of the intact holoprotein and penetrates the blood–brain barrier. In the current study, we utilized a murine model of transient focal cerebral ischemia and reperfusion to demonstrate that intravenous (IV) administration of COG1410 reduces infarct volume and radiographic progression of infarct, and improves functional outcome as assessed by rotarod when delivered up to 4h after ischemia onset. ► Intravenous administration of ApoE mimetic peptide COG1410 crosses BBB and is well tolerated. ► Administration of COG1410 improves functional recovery in a murine stroke model. ► COG1410 reduces neuroinflammation and secondary injury in a murine stroke model. ► Administration of ApoE mimetic reduces infarct extension after stroke on serial MRI.