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9254726 
Journal Article 
Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial 
Ritchie, CW; Bush, AI; Mackinnon, A; Macfarlane, S; Mastwyk, M; Macgregor, L; Kiers, L; Cherny, R; Li, QX; Tammer, A; Carrington, D; Mavros, C; Volitakis, I; Xilinas, M; Ames, D; Davis, S; Beyreuther, K; Tanzi, RE; Masters, CL 
2003 
Yes 
Archives of Neurology
ISSN: 0003-9942
EISSN: 1538-3687 
60 
12 
1685-1691 
English 
14676042 
WOS:000187178700003 
Alzheimer disease (AD) may be caused by the toxic accumulation of beta-amyloid (Abeta).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 Abeta, thereby promoting Abeta dissolution and diminishing its toxic properties.A pilot phase 2 clinical trial in patients with moderately severe Alzheimer disease.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 those taking placebo compared with minimal deterioration for the clioquinol group. Plasma Abeta42 levels declined in the clioquinol group and increased in the placebo group. Plasma zinc levels rose in the clioquinol-treated group. The drug was well tolerated.Subject to the usual caveats inherent in studies with small sample size, this pilot phase 2 study supports further investigation of this novel treatment strategy using a metal-protein-attenuating compound.