2026 年 12 巻 p. 34-38
Adrenomedullin (AM) is a vasoactive peptide with pleiotropic vascular actions beyond vasodilation, including endothelial protection, anti-oxidative and anti-inflammatory effects, and pro-angiogenic/arteriogenic activities mediated by VEGF/bFGF induction and PI3K/Akt activation. In mice subjected to chronic cerebral hypoperfusion, AM administration or genetic strategies that raise circulating AM levels promote collateral artery growth and capillary angiogenesis, leading to earlier recovery of cerebral blood flow, attenuation of white-matter injury, and improved cognitive performance—providing a rationale for clinical translation. In the AMFIS (AM For Ischemic Stroke) phase II trial in acute ischemic stroke, the safety of intravenous AM was confirmed. Subsequently, the AMCAD (AM for CADASIL) trial targeting the rare hereditary small-vessel disease CADASIL is underway, using arterial spin labeling (perfusion MRI)–derived changes in frontal cortical cerebral blood flow as the primary endpoint. For efficacy assessment in vascular cognitive impairment, it is crucial to visualize pharmacological effects using objective intermediate markers derived from perfusion imaging, diffusion tensor imaging of white matter, and blood biomarkers, in addition to clinical symptoms. Optimization of target populations by integrating perfusion/white-matter imaging with biomarkers may establish AM as a disease-modifying therapy for cerebral small-vessel disease and vascular cognitive impairment.
