Anavex Life Sciences Corp (AVXL)

[falconer66a]

Different, but effective.

Can we assume Anavex 2-73 works the same way for all three(Rett, PDD
and Alzheimer) by "Its activation of the protein causes the protein to
take on or resume modulation or facilitation of a number of homeostatic
processes in the neuron."?

Well, in regards to Anavex 2-73, quite a bit, by quite a number of posters, has been “assumed.” But, an important question. Let the findings from pre-clinical murine (lab rodent) studies, and early-stage human studies tell the story.

No, the mechanisms by which blarcamesine (Anavex 2-73) yields favorable therapeutic results in the three CNS diseases now being tested in human trials are not, cannot be the same. Particularly with Rett syndrome. It’s symptoms result from a genetic anomaly; bad genes. The condition is present at birth. The other two central nervous system diseases being tested, Parkinson’s disease dementia, and Alzheimer’s disease, are not present at birth; they appear much later in life, usually in the middle age period or later. Before that, neurons function adequately, with no cognition complications.

I am not familiar with the particular mechanisms blarcamesine uses to reduce Rett symptoms. Most likely its activation of the sigma-1 receptor protein causes the neuron to both detect biochemical anomalies (dysfunctions) and at the same time prompt the cell to try to suppress them. In general, that’s what happens in homeostasis. Blarcamesine promotes normalized homeostasis in neurons. Virtually all homeostatic processes (there are hundreds in the entire body) involve feedback mechanisms. The cell detects that something is going too strongly or weakly, so the feedback process either throttles it or increases it, back to a detected point of normalcy. The poor genetics of Rett cause various things to over- or under-perform. With blarcamesine, the cell can detect these anomalous conditions and prompt the appropriate feedback.

Rett syndrome is “X-linked,” meaning that the genes for the disease are on the X chromosomes. Males have one X and one Y chromosome; girls just two X’s, no Y’s. Boys who in utero have a Rett syndrome gene on their single X chromosome will die. The gene is lethal. Girls, with a Rett syndrome gene on one chromosome, have a normal, contrary gene on their other X. The good gene on the normal X chromosome works good enough for the girl to grow, but she has a host of neurological and physiological problems. Blarcamesine’s promotion of normal feedback processes, (autophagy) causes the cell to promote the activity of the good gene, and/or suppress the activity of the bad gene on the other chromosome.

A bit different with Parkinson’s and Alzheimer’s. In these, excess amounts of chemical wastes are either produced, or don’t get normally cleared. A waste disposal problem. The cell's garbage disposal starts to lose effectiveness. Waste proteins accumulate, and they interfere with the neuron’s normal function, the proper transmission of nerve impulses. When so disturbed, cognition is compromised.

The clearance of wastes, involved in the cell’s autophagy, clears away and re-processes the chemical wastes. “Auto-” means “self.” “-phagy” means to “eat.” When working normally, the neuron eats up (digests) its wastes, either expelling them or reprocessing them to smaller feedstock molecules used to make good molecules. Blarcamesine promotes or facilitates normalized autophagy. Wastes are properly cleared before they mess up normal neuron functions.

Also, blarcamesine promotes, facilitates proper protein folding, in the endoplasmic reticulum. The proteins there (mostly) are enzymes, biochemical catalysts that cause favorable reactions to occur. If catalysts get, literally, bent out of shape (misshapen), they can’t catalyze essential reactions. The cell fails to work well. Blarcamesine facilitates proper protein, enzyme folding. Consequent reactions can go forward. The neuron functions normally.

Blarcamesine does other good things, too. Astonishingly, it is able to properly unwind chromatin, a complex protein that wraps around chromosomes and protects them. In order for the genetics of a chromosome to be expressed, the chromatin must be properly and carefully removed. Not an easy task. Many genetic problems, particularly those appearing in older years (as with Parkinson’s and Alzheimer's) may also involve chromatin unwinding problems. Blarcamesine ameliorates those problems.

Blarcamesine. A single molecule too good to be true. Too many favorable but diverse mechanisms to think possible. However, a multitude of murine, and now human, clinical trials are revealing them. Others will appear. Let’s watch.