Apolipoprotein E mimetic peptide CN-105 may be safe and feasible for delirium prevention in older surgical patients

1. Apolipoprotein E Mimetic Peptide CN-105 was found to be safe and feasible among older patients with noncardiac or nonintracranial surgery.

Evidence Rating Level: 1 (Excellent)

Apolipoprotein E (APOE) gene ε4 allele is linked with neuroinflammation and is a potential risk factor for postoperative delirium. ApoE and apoE mimetic peptides, such as CN-105 may reduce delirium incidence by blocking neuroinflammation. CN-105 has been found to be safe and tolerable among healthy participants in two previous phase 1 MARBLE (Modulating ApoE Signaling to Reduce Brain Inflammation, Delirium, and Postoperative Cognitive Dysfunction) trials. This phase 2 MARBLE trial thus examined the safety and feasibility of CN-105 for reducing postoperative delirium and neuroinflammation in older surgical patients. This randomized clinical trial enrolled patients from April 17, 2019, to December 28, 2022, at a tertiary academic medical center in North Carolina, U.S., and included patients > 60 years older scheduled for a noncardiac or nonintracranial surgery. Patients were randomly assigned 3:1 to the CN-105 group or placebo group. The CN-105 group received intravenous CN-105 doses of 0.1, 0.5, or 1 mg/kg (3 cohorts). The primary outcome was the incidence and number of postoperative adverse events (AEs) at 6 weeks. In total, 186 participants were randomized and underwent surgery (mean [SD] age, 68.7 [5.2] years; 119 males [64.0%]), with 137 in the CN-105 group and 49 in the placebo group. The rates of grade 2 or higher AEs among patients between the CN-105 vs placebo groups were not significantly different (76.6% vs 87.8%; relative risk [RR], 0.87; 95% CI, 0.76-1.00). The CN-105 group had fewer grade 2 or higher AEs per patient compared to the placebo group (median [IQR], 1 [1-3] vs 2 [1-5]). The percentage of CN-105 doses administered within the time window was 94.6% (860/ 909; 95% CI, 92.9%-96.0%) in the CN-105 group and 93.8% (346/369; 95% CI, 90.8%-96.0%) in the placebo group, exceeding the prespecified feasibility threshold of >90%. Overall, this phase 2 trial found CN-105 to be safe and feasible among older patients with noncardiac or nonintracranial surgery. Future trials are needed to evaluate the efficacy of CN-105 for reducing postoperative AEs.

Click here to read the study in JAMA Network Open

Image: PD

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