early days, but could be good. (5.00 / 2) (#5)
by iGrrrl on Sun Jun 24, 2001 at 05:26:44 PM EST
An editorial comment asked whether this was good science. I think the work is reasonable. Will it cure Alzheimer's? Who can say? I read the original article in Neuron, which is considered a quite reputable journal, and they certainly seem to be onto something. The important caveats are that this is in a transgenic mouse model which overexpresses one of the proteins found in AD plaques, and that the plaques formed in this mouse differ in some biochemical ways from those formed in AD humans. Still, these mice suffer physical and cognitive defects with age, and these problems improved with the treatment.
From the introduction:
CQ [the chelator used in the study] was used extensively as an oral antibiotic (Richards, 1971 ) before it was withdrawn in the early 1970s due to
overdose-associated neurological side effects that are now believed to be preventable with B12 supplementation (Yassin et al., 2000 ).
There is some precidence for the use of chelators with AD, but the difference in this study was that they chose a compound which would cross the blood-brain barrier. There are a number of reasons why chelating metals would work, but I feel the need to point out that Zinc and Copper are necessary for proper brain function. The chelators actually increase the free Cu and Zn in the brain as compared to controls, probably by breaking up plaques which could be serving as metal sinks. So the plaques probably hurt two ways -- by causing physical damage and by changing the metal biochemistry of the brain.
Here we report the effects of CQ (oral treatment) on aged APP2576 Tg mice with advanced A-beta deposition. CQ treatment for 9 weeks
markedly inhibited cerebral A-beta deposition by 375 µg/g wet weight compared to sham-treated controls. These changes were accompanied by no
adverse effects and a significant improvement in scores on a general behavior rating scale. These findings are strong support for the role of
zinc and copper interaction with A-beta in the pathophysiology of AD and indicate that the CQ class of agents could have therapeutic utility in AD.
As for the human potential (quoting again from the original article):
A completed phase one clinical trial of CQ with B12
supplementation in AD patients revealed no adverse systemic, neurological, or cognitive effects (C.G. Gottfries and M.X., unpublished data).
So far it doesn't seem to hurt the patient (phase I trials are to screen for adverse affect, not benefit). Keep your fingers crossed on the possibility of benefit, but don't plan on seeing it advertised any time soon.
Neuron, Vol 30, 665-676, June 2001
Treatment with a Copper-Zinc Chelator Markedly and Rapidly Inhibits
-Amyloid Accumulation in Alzheimer's Disease Transgenic Mice
Robert A. Cherny, Craig S. Atwood, Michel E. Xilinas, Danielle N. Gray,
Walton D. Jones, Catriona A. McLean, Kevin J. Barnham, Irene Volitakis,
Fiona W. Fraser, Young-Seon Kim, Xudong Huang, Lee E. Goldstein, Robert
D. Moir, James T. Lim, Konrad Beyreuther, Hui Zheng, Rudolph E. Tanzi,
Colin L. Masters, and Ashley I. Bush
You cannot have a reasonable conversation with someone who regards other people as toys to be played with. localroger
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