Clioquinol for the treatment of Alzheimer's Disease
Abstract
Background
Alzheimer's disease (AD) may result in senile plaques being formed outside the brain as accumulation of beta‐amyloid (Aß).
Objectives
To evaluate the efficacy of clioquinol for the treatment of cognitive impairment due to Alzheimer's disease.
Search methods
The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 20 May 2005 using the terms clioquinol and PBT1. The Register contains records from major health care databases and many ongoing trial databases and is updated regularly. The Internet was searched using the term: clioquinol PBT1 Alzheimer*.
Selection criteria
Randomised double‐blind trials in which treatment with clioquinol was administered to participants with Alzheimer's disease in parallel group comparison with placebo are included.
Data collection and analysis
Two reviewers (RM, LJ) independently assessed the quality of trials according to the Cochrane Collaboration Handbook.
The primary outcome measures of interest were cognitive function (as measured by psychometric tests) and global impression. The secondary outcome measures of interest were in the following areas: quality of life, functional performance, effect on carer, safety and adverse effects, and death.
Main results
There was one included trial of clioquinol compared with placebo in 36 patients.
Authors' conclusions
It is not clear from the trial that clioquinol shows any positive clinical result on patients with AD. The two statistically significant positive results were seen for the more severely affected subgroup of patients. This effect was not maintained at the 36 week end‐point. The sample size was small. Details of randomisation procedure or blinding were not reported. Further studies are needed to evaluate the potential for clioquinol as a treatment of AD. Trials of longer duration are also required, particularly because information about the side‐effects of long‐term use of clioquinol is limited.
Since publishing this review, Prana Biotechnology has discovered that its manufacturing process of clioquinol PBT1 contained certain mutagenic "di‐iodo" PBT1 impurities that could not be reduced to an acceptable level. Prana has suspended PBT1 development. Prana Biotechnology is now developing PBT2, a successor compound to PBT1 for Alzheimer's disease and began a Phase I human clinical trial in March 2005. The authors of this review are preparing a new review on this PBT2 successor compound. PBT1 (Clioquinol) is now obselete.
PICOs
Plain language summary
There was no convincing evidence from the one available trial of the efficacy of clioquinol for the treatment of Alzheimer's disease (AD).
Alzheimer's disease is a progressive disease of the brain that is characterized by impairment of memory and a disturbance in at least one other thinking function (for example, language or perception of reality). Clioquinol is a chelator that crosses the blood‐brain barrier and has great affinity for copper and zinc ions. As heavy metals ions may be implicated in the formation of senile plaques in Alzheimer's disease, treatment with clioquinol may retard the progression of this disease by inhibiting copper and zinc ions from binding to beta‐amyloid. This may in turn promote dissolution of beta‐amyloid and diminish its toxic properties. Since publishing this review, Prana Biotechnology has discovered that its manufacturing process of clioquinol PBT1 contained certain mutagenic "di‐iodo" PBT1 impurities that could not be reduced to an acceptable level. Prana has suspended PBT1 development. PBT1 (Clioquinol) is now obselete.
