right drug - wrong dose ?

most didnt respond well to this when it came out after Reach2HD results as we were all on cloud 9, but interesting to re-read now after Imagine results.

http://seekingalpha.com/article/2062823-prana-right-drug-wrong-dose

"Given the available data, I expect a mixed result from the IMAGINE trial. There may be some minimal cognitive benefit, but it will be apparent only with data contortions - perhaps a peculiar subgroup analysis, or a semi-acceptable statistical test. We are quite likely to see a decrease in CSF Abeta 1-42 levels, as in the Phase 2a data, but the magnitude of the decrease will probably be small. A small, borderline-significant decrease in amyloid on PiB PET scans is likely. I predict that there will be no difference in brain volume by MRI and probably no difference in fluorodeoxyglucose PET imaging. I consider it very unlikely that IMAGINE will have a powerful, incontrovertible result that will suffice for drug registration, and moderately improbable that the data will be strong enough to convince Prana's many doubters.
The best move for Prana after the results will be to measure the PBT2 levels in the CSF samples from the IMAGINE trial. Alternatively, subgroup analysis suggesting better efficacy in underweight or hypoalbuminemic patients could suggest that underdosing is taking place. If the levels of free PBT2 in the CSF are low (as I expect them to be), Prana should perform a short-term dosing trial in which the company identifies a higher safe dose. Such a trial could be performed in a few months at minimal cost. It need not be large, nor would such a trial need to include expensive PET scans. However, CSF sampling, possibly with tritiated or carbon-14 labeled drug, would be advisable to prove that adequate drug concentrations are being obtained in the CNS."