BB- Colin Masters was already on to the ApoE4 gene issue as...

BB- Colin Masters was already on to the ApoE4 gene issue as indicated in this post from alzforum:

Colin Masters University of Melbourne Posted: 11 Apr 2014 The IMAGINE study conducted by Prana Biotechnology was a small (n=42) exploratory trial supported by a grant from the Alzheimer’s Drug Discovery Foundation to see if the novel 8-OH quinoline (PBT2) would have an effect on Aβ-amyloid burden as reported by PiB-PET neuroimaging over 12 months. Secondary objectives included MRI volumetry, FDG-PET, cognitive change and Aβ-related blood biomarkers. The draft preliminary results indicated a surprising fall in the PiB SUVRs in the placebo group, which obscured any statistical separation from the drug treatment group (which also showed a larger decrease). I agree with most of the comments from Lon Schneider, Bruno Pietro Imbimbo, and Susan Landau. I would prefer to reserve judgement on the study until all the data have been verified, analysed and publicly released, particularly the effect of the ApoE4 polymorphism and the changes in blood biomarkers (especially Aβ dimers). It's worth noting that the IMAGINE trial is still ongoing in an open-label extension study that will conclude in early 2015, and that the overall safety data from the IMAGINE trial so far is excellent. Further independent support for the use of this class of drug has come from unbiased screens of Aβ-toxicity (Matlack et al., 2014). Indeed the scientific argument for this therapeutic approach has become more compelling with published data for PBT2 demonstrating its reduction of tau protein, upregulation of synaptic plasticity markers, and reduction of Aβ-induced synaptotoxicity (Adlard et al., 2008). It is far too premature to abandon this clinical approach of proof-of-concept. As Lon comments, a reasonable development program would have entailed a much larger study, but unfortunately the funds for this are yet to be sourced. Lon's further analogy with a Hail Mary pass invites the rebuttal that the effort was more like an Our Father, or even The Credo: “I believe in one principle, the almighty Aβ, cause of all Alzheimer's disease, both clinical and preclinical." For those who appreciate that an n=42 PiB study does not portend the doom of this novel therapeutic, it is hoped that there are others who understand that the real test and opportunity for PBT2 in Alzheimer’s disease lies in an appropriately powered trial to explore clinical benefit.