Donepezil "might" be competing? 2-73 is a competitive agonist for the sigma receptor. It competes for that receptor site. Most these patients (mild to mod) have been on dzp a long time and we know beyond 3 months, it stops improving patients scores. So, dzp is occupying those receptors without doing anything of benefit after 3 months to a year. Those receptors could have been occupied by 273. Which has greater affinity for sigma 1, dzp or 273? DZP's affinity is 14.6. What is 273's affinity? IDK. You tell me
I don't doubt 273 and dzp had synergy in the mouse study. Why? Because in the mouse study the dzp was actually helping not just sitting there. Why? Because the mice were put on it fresh, for the first time, at the same time they were put on 273. That didn't happen in the clinical study. The design of the mice and human studies were not the same. If the subjects were put on dzp fresh when they started 273, I think we'd see improvement similar to the mouse study. But that synergy only lasts so long as dzp's beneficial affect overcomes the disease's progression.
When comparing this trial to others, make sure you're comparing apples to apples. Is the patient population the same? Other studies (cough, aducanumab) use prodromal patients that aren't that sick or progressed with Alzheimers. They do this to pad their results. They also use huge n's, which reduces risk. They put patients on the max dose tolerated that is deemed therapeutic. Did anavex do any of this for their trial? No. Does 273 cause severe brain swelling or raunch someone's gastrointestinal tract? No. The MMSE overall score was stable from baseline, that is what I referred to. In the 7 montherapy subjects is has risen at 31 weeks. That is not, as you said, BS.
