Designed to modify the course of AD by preventing metal-
dependent aggregation, deposition, and toxicity of Aβ
(Ritchie et al., 2003). Aβ is a high-affinity metal
binding protein which adopts a toxic gain of function in
the presence of copper and zinc. PBT2 acts at three levels
of the “amyloid cascade”: it inhibits the redox-dependent
formation of toxic soluble oligomers, prevents deposition
of Aβ as amyloid plaques, and promotes clearance by
mobilizing and “neutralizing” Aβ from existing
deposits (Cherny et al., 2001).
A 12 week Phase IIa study testing safety and efficacy of
PBT2, with biomarker analysis, in a double-blind,
randomized, placebo-controlled trial showed that treated
patients had a dose-dependent and significant reduction of
CSF Aβ, and demonstrated significant improvement in two
tests of executive function: the category fluency test and
trail making part B test (Lannfelt et al., 2008).
The parent compound clioquinol (PBT1) was tested in
clinical trials for AD. It was not clear from this trial
that clioquinol showed any positive clinical result. The
two statistically significant positive results were seen
for the more severely affected subgroup of patients;
however, this effect was not maintained at the 36-week end-
point, and this group was small (eight treated subjects).
The sample size was small. Details of randomization
procedure or blinding were not reported (Jenagaratnam &
McShane, 2006).
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