Can clioquinol slow the progression of Alzheimer's Disease?

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Offline Ylide

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Some study showed that the 100 year old drug clioquinol (used as an anti-fungal, i believe) can prevent the accumulation of copper and zinc in the brain, halting the progress of dementia.  

Apparently, they believe that these metals bond with a certain protein in the brain and converts oxygen to hydrogen peroxide, which is toxic to brain cells.  I'm not sure of the mechanism of how this works, nor how the drug works...maybe one of the medical types can explain?
« Last Edit: 16/06/2008 12:16:06 by chris »
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Offline chris

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Can clioquinol slow the progression of Alzheimer's Disease?
« Reply #1 on: 20/06/2008 11:50:57 »
This suggestion is based on a paper published in December 2003 in Archives of Neurology (Arch Neurol. 2003;60:1678-1679, 1685-1691).

In this paper, which documents a phase II trial of the agent, 36 Alzheimer's patients with moderately severe symptoms were randomised to receive either clioquinol or a placebo. Cognitive scores and blood levels of the protein linked to Alzheimer's, beta-amyloid, were followed up over the next 36 weeks.

The results showed a reduction in beta-amyloid and an arrest in cognitive decline amongst the patients receiving the active treatment, compared with a continued decline amongst the placebo group.

Clioquinol works by blocking the binding of zinc and copper to beta-amyloid, thereby preventing its aggregation.

This summary provides a more thorough overview:

However, a review published by the Cochrane Collaboration in 2007 failed to find any evidence of net benefit. Their findings were:

"There was one included trial of clioquinol (PBT1) compared with placebo in 36 patients. There was no statistically significant difference in cognition (as measured on the ADAS-Cog scale) between active treatment and placebo groups at 36 weeks. One subject in the active treatment group developed neurological symptoms (impaired visual acuity and colour vision) which resolved on cessation of treatment and was thought to be possibly attributable to the drug.

Authors' conclusions
There is an absence of evidence as to whether clioquinol (PBT1) has any positive clinical benefit for patients with AD, or whether the drug is safe. We have some concerns about the quality of the study methodology, particularly the randomisation (subjects in the active treatment group had higher mean pre-morbid IQ as measured by the NART and this may have biased the results), the secondary analyses of results stratified by baseline disease severity and whether the study was adequately powered for the analysis of the other data collected on Aß, zinc and copper levels."


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