Replies to post #343401 on Anavex Life Sciences Corp (AVXL)

[falconer66a]

Anavex 3-71 Against Alzheimer’s

AF710B [Anavex 3-71] long-term treatment reverted the cognitive deficits associated with advanced Alzheimer-like amyloid neuropathology in Tg rats [McGill-R-Thy1-APP transgenic Alzheimer’s rats]. These effects were accompanied by reductions in amyloid pathology and markers of neuroinflammation and increases in amyloid cerebrospinal fluid clearance and levels of a synaptic marker. Importantly, these effects were maintained following a 5-week interruption of the treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232171/#B88-ijms-22-06359

Let me interpret what is stated in this abstract of a study of Anavex 3-71 in transgenic (gene-inserted) rats with consequent Alzheimer’s disease.

Treatment with Anavex 3-71 was “long-term,” not for just a few days or so. Most significantly this dosing “reverted the cognitive deficits associated with advanced Alzheimer-like amyloid neuropathology.” Simply, the rats had advanced cases of Alzheimer’s, but the Anavex drug “reverted” the “cognitive deficits.” The disrupted or disturbed thinking abilities of the rats were turned around. At the end of treatment their cognitive abilities tended toward normal.

What would be the impact if that were to happen in humans with Alzheimer’ disease? Appears very obvious, then, that if Anavex 3-71 treatment were begun at the first diagnosis of Alzheimer’s, cognition could be “reverted” back to normalcy.

Then, “these effects were maintained following a 5-week interruption of the treatment.” What does that mean? First, five weeks in the life of a rat would be equivalent to many months or several years in a human. “One rat month is comparable to three human years.”
https://www.researchgate.net/publication/268409698_The_Laboratory_Rat_Relating_Its_Age_With_Human's

Five rat weeks would then be equivalent in humans to about 3 yrs, 9 months. Imagine, taking a drug that prevents or reverses Alzheimer’s for a useful period, say six months, then going off it for over three years while it continues to work. The take-away is this. Anavex 3-71 binds to the sigma-1 receptor protein and stays attached for lengthy periods of time, all the while modulating and facilitating favorable cell processes.

It is then very plausible that if/when Anavex 3-71 becomes available as a CNS disease therapeutic, after an initial “loading dose” treatment period, the drug will be taken intermittently, at yet to be determined longer intervals. Perhaps subsequent dosings will be each week, on Mondays and Tuesdays.

Clearly, the drug is not rapidly cleared from the cell. In cellular autophagy Anavex 3-71 is chemically regarded as a normal endogenous cellular chemical; not a waste or toxin that must be cleared.

Additionally, as mentioned previously, Anavex 3-71 is dosed in microgram, not milligram masses. A milligram is a thousandth of a gram, a millionth of a gram. Anavex 3-71 doses are a thousandth of those of Anavex 2-73 (blarcamesine). Not much is needed. It readily crosses the blood-brain barrier and enters cells, where, as this study shows, it is not digested or excreted as a waste or toxin.

Coupled with the drug’s profound efficacies and safety, nothing more could be hoped for. An ideal drug, dare I project.

Of course, for human therapeutics all of this will have to be tested and proved in proper clinical trials, some years away. First, it will be blarcamesine in the on-going Phase 3 Alzheimer’s trial. That will not be end of Anavex clinical trials for Alzheimer’s. Anavex 3-71 will be called up from the minor leagues to see how it can play in the Alzheimer’s big leagues. As above, all pre-clinical data are profoundly favorable. In 2022 and 2023 blarcamesine will be the Anavex star. After that, and even better, will be Anavex 3-71.