RespireRx Pharmaceuticals Inc (RSPI)

[neuroinv]

While an interesting point, I don't think that is the case. Populations who have depression, schizophrenia, or are elderly would most likely not have optimal synaptic transmission, and thus would not run into the ceiling effect you are suggesting.

We are reinventing the wheel here. Human populations do not perform predictably on this kind of relatively soft testing (as opposed to harder lab value endpoints that don't really exist in CNS). There is a reason that everyone runs duration studies, they hope to eliminate some of variance that plagues these trials, but not always successfully.

An example--Targacept ran its own 16 week duration trial for its nicotinic agonist TC-1734, and reported remarkably robust efficacy data in a mild, AAMI population (where the upside potential would seem limited). AstraZeneca partnered, ran a much larger trial in Alzheimer's, with a three month treatment duration, and the results were negative. Interestingly, they were negative not only for TC-1734/AZD3480, but also for Aricept, which was used as an active comparator.

AZ has spent months since trying to figure out why. The drug completely washed out in schizophrenia. Now they are waiting for ADHD (!) results to figure out whether to kill the drug or not. And it's this kind of unpredictable, seemingly contradictory pattern of results which makes CNS disorders so difficult.

NeuroInvestment