The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative...

Area of Science:

• Geriatric Medicine
• Neuroscience
• Pharmacology

Background:

• Perioperative neurocognitive disorders (PND) are common in older adults, increasing mortality and long-term cognitive decline.
• The Alzheimer's disease (AD) genetic risk factor APOE4 is linked to PND, potentially via neuroinflammation.
• The efficacy of modulating APOE4 signaling to reduce PND risk is unknown.

Purpose of the Study:

• To evaluate the safety and feasibility of perioperative CN-105 administration in older adults.
• To assess the efficacy of CN-105 in reducing perioperative neuroinflammation and PND severity.
• To gain insights into the pathogenesis of geriatric syndromes like PND.

Main Methods:

• MARBLE trial: a randomized, blinded, placebo-controlled phase II dose escalation study.
• 201 patients (age ≥60) received CN-105 or placebo perioperatively.
• Evaluations included adverse events, cognition, delirium, and neuroinflammation markers (blood/CSF).

Main Results:

• Primary endpoint: safety and adverse event rates of CN-105 vs. placebo.
• Secondary endpoints: feasibility, neuroinflammation, and PND severity.
• Results will be disseminated via conferences and publications.

Conclusions:

• The MARBLE study assesses CN-105 for PND prevention in older surgical patients.
• It aims to elucidate the role of APOE4 and neuroinflammation in PND pathogenesis.
• Findings will guide future therapeutic strategies for cognitive complications after surgery.