I would like to ask Dr. Bush whether there is any evidence that clioquinol may inhibit SOD1 activity?
Lee et al.(1) find that the neuronal adaptor protein X11α reduces Aβ levels. McLoughlin et al.(2) find that X11α interacts with the copper chaperone for SOD1 to inhibit to SOD1 activation.
Were clioquinol to inhibit SOD1, would it then enable X11α to have a more active role in Aβ reduction?
Does the fact that thiamine inhibits SOD1 as reported by Lee et al.(3) explain the similarities in the pathology of thiamine deficiency and AD?
(1) Lee JH, Lau KF, Perkinton MS, Standen CL, Shemilt SJ, Mercken L, Cooper JD, McLoughlin DM, Miller CC. The neuronal adaptor protein X11alpha reduces Abeta levels in the brains of Alzheimer's APPswe Tg2576 transgenic mice. J Biol Chem. 2003 Nov 21;278(47):47025-9. Epub 2003 Sep 11. Abstract
(2) McLoughlin DM, Standen CL, Lau KF, Ackerley S, Bartnikas TP, Gitlin JD, Miller CC. The neuronal adaptor protein X11alpha interacts with the copper...
This study is interesting and provocative. Having said that:
1. the sample size is very small;
2. the main effect on the ADAS-cog was nonsignificant;
3. the effect in the group with more severe AD may be driven by only a few subjects
since the group had only about eight subjects in the clioquinol and eight in the placebo group;
4. why plasma Aβ levels rose in the placebo group is mystifying;
5. studies of acetylcholinesterase inhibitors and memantine all used substantially larger sample sizes. However, these were funded by pharmaceutical companies, not a small biotech company such as Prana;
6. clioquinol is not benign—one person (of 16 exposed) developed impaired color vision.
In sum, these data warrant a larger study.
View all comments by Leon Thal