Metal-Protein Attenuation with Iodochlorhydroxyquin (Clioquinol) Targeting Aβ Amyloid Deposition and Toxicity in Alzheimer Disease: A Pilot Phase 2 Clinical Trial

Abstract

Background: Alzheimer disease (AD) may be caused by the toxic accumulation of β-amyloid (Aβ). Objective: To test this theory, we developed a clinical intervention using clioquinol, a metal-protein-attenuating compound (MPAC) that inhibits zinc and copper ions from binding to Aβ, thereby promoting Aβ dissolution and diminishing its toxic properties. Methods: A pilot phase 2 clinical trial in patients with moderately severe Alzheimer disease. Results: Thirty-six subjects were randomized. The effect of treatment was significant in the more severely affected group (baseline cognitive subscale score of the Alzheimer's Disease Assessment Scale, ≥25), due to a substantial worsening of scores in tho..