title: Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta 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 beta-amyloid (Abeta).
  
  
  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 Abeta, thereby promoting Abeta 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Pathology, The University of Melbourne, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Ritchie
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: Andrew
authors.initials: A
authors.lastname: Mackinnon
authors.forename: Steve
authors.initials: S
authors.lastname: Macfarlane
authors.forename: Maree
authors.initials: M
authors.lastname: Mastwyk
authors.forename: Lachlan
authors.initials: L
authors.lastname: MacGregor
authors.forename: Lyn
authors.initials: L
authors.lastname: Kiers
authors.forename: Robert
authors.initials: R
authors.lastname: Cherny
authors.forename: Qiao-Xin
authors.initials: QX
authors.lastname: Li
authors.forename: Amanda
authors.initials: A
authors.lastname: Tammer
authors.forename: Darryl
authors.initials: D
authors.lastname: Carrington
authors.forename: Christine
authors.initials: C
authors.lastname: Mavros
authors.forename: Irene
authors.initials: I
authors.lastname: Volitakis
authors.forename: Michel
authors.initials: M
authors.lastname: Xilinas
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.forename: Stephen
authors.initials: S
authors.lastname: Davis
authors.forename: Konrad
authors.initials: K
authors.lastname: Beyreuther
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000097:blood; D002614:Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007464:Clioquinol / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition; D003300:Copper / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010865:Pilot Projects; D012720:Severity of Illness Index; D015032:Zinc / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D003300:Copper; D007464:Clioquinol; D015032:Zinc