Not a very smart comparison, but the number of patients was in Dimebon study 403, so some 200 in the two groups. In PBT2 study placebo, 100mg and 250mg groups have 34-35 patients each. Treatment time is same, 26 weeks. Dimebon had no effect and it was perhaps known that the effect is not great when the study was started and to show any effect at least 200 patients was needed. Did not help, no effect.
In reach2HD, the hopes are higher and so are the numbers smaller. As I told earlier Reach2HD study is only designed to demontrate improvement. If you look at the Cherny's mouse study the difference was clear after 4 weeks treatment by using only 10 mice in each group. So PBT2 looks good in HD mice.
It is also looking at biomarkers. I dont think there is as much longitudinal date available for Huntingtons biomarkers as for Alzheimer's. I know the recent work on iron levels will probably be a valuable biomarker in Huntington's progression and onset. With any luck this trial will demonstrate a reversal of that iron build up trend.
Cherny in the HD mouse study paper :" PBT2 is being developed as a potentially disease modifying drug for AD and HD".
" therapeutic effects of metal chaperones likePBT2 are thought to be due to intervention in multiple pathological events resulting from metal dyshomeostasis including inhibition of metal mediated oxidative damage, intervention in the aggregation process and restoration of neuronal function".
To me it looks like the accumulation of iron (causing oxidative damage) could be reversed by PBT2 (remember the Bush paper in Cell), aggregation of mHtt (mutant Huntington protein) could also be reversed by PBT2 by reducing Cu needed to make it's monomers to toxic dimers (the paper by J Fox 2011).
Cherny tells also in this paper that " improved cognition with PBT2 in animal models has now been shown to correlate strongly with elevated markers of neuronal function and plasticity including NMDAr,TrKb, proBDNF, BDNF, CAMkII, spinophillin and synaptophysin as well as signiﬁcant increases in hippocampal dendritic spine density" (paper by Adlard et al in 2011).
There was nothing like this type of information about the effect of Dimebon.
So if these facts seen in animals will be true also in humans, we will get positive results in the Reach2HD study. We will have the results perhaps in 2-3 months but latest in Oct.