title: Metal-protein attenuating compounds and Alzheimer's disease.
abstract: Since the description of the amyloid plaque in the pathology of Alzheimer's disease, one of the main focuses of research has been the role of the amyloid precursor protein metabolite amyloid-beta, which is the constituent protein of plaque. Affecting the production, aggregation or clearance of this protein may well have a modifying effect on disease progression. Although available therapies for Alzheimer's disease may interact with amyloid-beta in vivo, no conspicuous disease-modifying effect has been demonstrated in clinical trials with these drugs. Drugs whose primary target is not the rectification of the neurotransmitter deficits associated with Alzheimer's disease but rather the life cycle of amyloid-beta are currently being developed with varying degrees of success. Of these drugs, the metal-protein attenuating compounds have currently the most encouraging clinical data supporting their use. Clioquinol is an example from this class, which has recently shown encouraging efficacy from early clinical evaluation in the absence of any compelling evidence of subacute myelopathic optic neuritis, which has been associated with this drug's use in Japanese populations. This article will discuss the scientific rationale behind the use of metal-protein attenuating compounds in Alzheimer's disease and summarise the available clinical trial data.
authors.affiliation: Royal Free and University College Medical School, Metabolic and Clinical Trials Unit, Department of Mental Health Sciences, Royal Free Campus, University College London, Rowland Hill Street, London, NW3 2PF, UK. c.ritchie@medsch.ucl.ac.uk
authors.forename: Craig W
authors.initials: CW
authors.lastname: Ritchie
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D007464:Clioquinol / Q000627:therapeutic use*; D006801:Humans; D051379:Mice
chemical_list: D016229:Amyloid beta-Peptides; D007464:Clioquinol