The protein amyloid-β (Aß) is strongly implicated in the development of Alzheimer's dementia, where it aggregates in clumps causing damage and death of brain cells. This clumping is encouraged by copper and zinc (metal ions) in the brain. Metal protein attenuating compounds (MPACS) bind strongly to copper and zinc (this is known as chelation), both preventing the clumping together of Aß and promoting processes which may cause it to dissolve and so be cleared from brain cells. Therefore MPACS may be a potential therapy for Alzheimer's dementia. Two different types of MPAC have been used in clinical trials and the drugs are known as PBT1 and PBT2. The trial of PBT1 compared with placebo (in 36 patients) showed no statistically significant difference in cognition or memory between the active treatment and placebo groups at 36 weeks. We therefore conclude that there is no current evidence that treatment with clioquinol (PBT1) has any significant effect on cognition and in particular memory (as measured by the ADAS-Cog scale) in patients with Alzheimer's dementia. This drug has now been withdrawn from development. The trial of PBT2 showed it was safe after 12 weeks of treatment but demonstrated no overall significant effect on cognition or memory.
There is no evidence that MPACs (PBT1 or PBT2) are of benefit in Alzheimer's dementia
21 February 2014
This record should be cited as:
Sampson EL, Jenagaratnam L, McShane R. Metal protein attenuating compounds for the treatment of Alzheimer's dementia. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD005380. DOI: 10.1002/14651858.CD005380.pub5
Assessed as up to date:
9 February 2012
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