Anavex Life Sciences Corp (AVXL)

[frrol]

It is a tough paper to follow, since it uses the term "modulation" often without specifying 'increase/decrease' or 'activate/silence'. But there are instances where it does, and the conclusion appears to be the opposite. As the paper states:

"We demonstrated that silencing of S1R expression reduces MAMs [and] reduces the levels of palAPP... MAMs and palmitoylation of APP directly modulate ß-secretase cleavage of palAPP and subsequent Aß generation...

"The observation that S1R activation and inactivation oppositely modulate the stability of palAPP...is consistent with previous studies..."

However, the paper has errors: "A previous study reported that S1R knockout only reduced MAM-assemblies in neurons by >50%, suggesting that more than half of MAM-assemblies were independent of S1R activity." This makes no sense as written.

So the paper is not clearly written, and in some places is downright sloppy. That happens.

According to most lab research to date, S1 agonism reduces Aß in neuronal cell cultures and animal models. This paper appears to contradict that, but it's not clearly written.

And in the end, this is why clinical trials are so important. Preclinical support is nice. But it's what the drug does in humans, with real disease, that matters. Hopefully folks are really seeing this now.