Anavex Life Sciences Corp (AVXL)

[falconer66a]

Very likely, very positive.

...what do you think the chances are for all three disease trials to go in one direction versus trials going in separate directions?

Good question.

The three diseases currently in human trials, a) Rett syndrome, an epigenetic disease of girls, b) Parkinson's disease dementia, and c) Alzheimer's disease, in one sense are all related; they are all diseases of the central nervous system (CNS). On the other hand, they are distinctly different from each other, at least in regard to symptoms. So, which will (or can) it be? All three trials turn out well, with positive outcomes; even though they are each very different diseases? Or, because they are so different, only one or none of them yield positive therapeutic outcomes from blarcamesine, the Anavex drug being tested?

On the face of it, considering that symptoms of each disease are distinct and different from the other two, it would seem chances of being able to successfully treat them all with a single drugs would be remote. Especially because the diseases are in the CNS. CNS diseases are, by themselves, difficult to treat. Fixing biochemical problems in brains, nerves, and neurons are difficult. "Brain science," as it were. Very, very complicated chemistries and cellular morphologies and reaction pathways and sequences. How could one single molecule fix the differing, complex biochemical anomalies of three very different CNS diseases? For that to happen, something special (and unique) must be at play.

With Anavex 2-73 (blarcamesine), such a thing is. It's the sigma-1 receptor protein, which, when activated (exactly what blarcamesine does) it causes a number of essential biochemical functions to operate normally in the neuron. In brief, properly activated sigma-1 receptor proteins cause the mitochondria to which they are in contact to operate normally, producing adequate amounts of ATP (adenosine triphosphate). ATP is the almost universal, essential energy-providing molecule that drives most energy-requiring reactions in cells. Insufficient ATP compromises or stops any number of reaction pathways; with pathogenic results.

With its activation of the sigma-1 receptor protein, blarcamesine also properly, favorably moderates calcium ion transport and exchange within the neuron; crucial for proper neuron functions.

Then, with both of those outcomes (and others), two utterly crucial neuron functions are supported or restored: a) ATP-powered folding of proteins in the endoplasmic reticula, which become the enzymes that catalyze virtually all chemical reactions in the cell, and b) support of autophagy, the ability of cells to "self-eat," whereby both wastes and poorly-formed molecules are "eaten up," destroyed and their chemical constituents recycled or expelled.

The key for blarcamesine (and CNS diseases) is this. By fixing the biochemical anomalies of the three diseases — which are based at or caused by sigma-1 protein dysfunction — this one molecule is able to treat the three very different diseases. Symptomatically, they are different. But all three produce bad symptoms because of inadequate activation of the sigma-1 receptor protein. Uniquely, blarcamesine can do that.

Well, then, if that's so, wouldn't there be a good number of other diseases for which sigma-1 receptor activation might work? Exactly. Go to the Anavex Life Sciences Corp Pipeline webpage; see the diversity of diseases and conditions Anavex is publicly stating they are addressing.

Personally, I'm certain that the number of diseases which in the future will be tested by Anavex is much, much larger. Sigma-1 receptor proteins are found in most cells and tissues in the body. If they don't work, all sorts of pathologies result. I base my conjecture on the good number of papers published on the use of blarcamesine against diseases in transgenic murines (rats and mice).

This includes my own CNS disease, hereditary spastic paraplegia (HSP), a condition where insufficient gamma-aminobutyric acid (GABA) is produced in long motor neurons to my legs. The GABA deficiency causes some nerves to some muscles in my legs to be hyperactive; always in tension. I walk with a walker, but can no longer walk up a staircase. When blarcamesine is approved for any sort of disease and becomes available, I will convince my neurologist to prescribe it to me, off label. The little girls with Rett had their GABA levels increase significantly in just a few weeks of blarcamesine. I'll pay the big bucks for the drug, and with the guidance of my neurologist will titrate dosages to an effective level. I have good reason to believe that with a few weeks or months of blarcamesine, I'll once again be able to walk normally. An existing treatment for HSP is the continuing injection of GABA into the spine (by an internal device). Expensive, hard to install and control. I'm eager for blarcamesine to naturally restore normal GABA production in my spine; exactly as it has for some transgenic rats with HSB genes. After drinking water with it for a few weeks, the rats lost all spasticity; ran inside the exercise wheel with vigor.

Let me summarize the matter. Unlike other CNS disease treatments, blarcamesine does not target or treat symptoms. Those occur "downstream" in the complex sequence of chemical reactions causing CNS pathologies. Instead, blarcamesine fixes upstream, at-the-start biochemical anomalies, starting at the sigma-1 receptor protein. Make that molecule function normally and a wide variety of good, downstream reactions result.

So, I believe blarcamesine will be successful for all three CNS diseases currently being tested (the three clinical trials). The mechanism(s) by which this could occur, starting with the sigma-1 receptor protein, are clear.