Anavex Life Sciences Corp (AVXL)

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Why Anavex Is Different

A consideration of how and why blarcamesine (Anavex 2-73) and Anavex 3-71 are markedly different CNS and other disease therapies.

First, the two major disease therapy targets for the Anavex drugs, Alzheimer’s and Parkinson’s diseases, are diseases or conditions that present themselves, have their onsets later in life. In most cases, people with the targeted diseases were in health in the first portions of their lives. Then, at middle or older age, any of the various disease symptoms appeared. In regard to the unique mechanisms of action (MOAs) of the Anavex drugs (which, among other things, are sigma-1 receptor protein activators), this is extremely significant.

Let’s start with Alzheimer’s disease. Twelve-year olds don’t get the disease. A very few, with a particular genetic propensity get it starting in their twenties or thirties. The vast majority first experience the disease’s symptoms after middle age, starting in the fifties, sixties, or seventies. Most commonly, Alzheimer’s is a geriatric disease, occurring in older people.

The same is true for the various forms of Parkinson’s disease.

With this typical scenario of symptomatic initiation, how can the Anavex drugs work, particularly in comparison to recognized and commonly used SOC (standard of care) drugs? Will the Anavex drugs treat these CNS (central nervous system) diseases the same way as conventional, existing drugs, or not?

Very much, not.

First, a diagnosis of either Alzheimer’s or Parkinson’s disease is ominous. Conventional, available treatments can only slow the lethal progression of those diseases. And most often, not very successfully. Simply, none of the existing drugs are able to effectively or safely restore a youthful, healthful state of neuron (nerve-cell) physiology. Although some welcome treatment outcomes may happen, the underlying, causative neuropathology lethally continues. Existing drugs for Alzheimer’s or Parkinson’s inevitably fail. Patients die.

How, then, could this be different with the Anavex drugs? How could they terminate or chronically suppress the disease-causing biochemical anomalies in each of the two big CNS diseases? No other drugs have been able to do this. Specifically, how can the Anavex drugs make this happen?

The key? Unique, propitious activation of the sigma-1 receptor protein. Anavex 2-73 (blarcamesine) and Anavex 3-71 easily cross the blood/brain barrier, enter neurons, and then bind to the sigma-1 receptor protein on the surface or edge of the endoplasmic reticulum. With that, all sorts of good things are initiated in the neuron.

When properly functioning or activated, the sigma-1 receptor protein (the Sig-1R) modulates, controls a diversity of processes within the neuron. “...Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in living systems.”
https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(16)00004-3.pdf

Simply, activation of the sigma-1 receptor by the Anavex drugs fixes bad things happening in diseased neurons. They restore “homeostasis,” the ability of the cell to properly control its biochemical function in a steady state, the “homeo-” process.

In the case of neurons with Alzheimer’s or Parkinson’s, homeostasis (“same status”) no longer occurs. In the case of Alzheimer’s, waste proteins, beta-amyloids or tau plaques, accumulate, disrupting normal nerve cell signaling and operation. Alzheimer’s symptoms result (cognitive impairment, etc.). In Parkinson’s, other biochemical disruptions occur — all because neurons can no longer work as they did in more youthful years. Activation of the sigma-1 receptor by either of the Anavex molecules restores normalized homeostasis.

One of the most important and significant outcomes of Anavex sigma-1 receptor activation is the proper folding of various enzyme proteins. Virtually every chemical reaction within a living cell is controlled and modulated by a specific enzyme. Enzymes are proteins, complex and detailed key-like structures. Like a key, if they get bent out of shape (as can happen in older age), they can’t catalyze chemical reactions. This happens in neurons being clogged with beta-amyloid waste proteins. Normally, enzymes are synthesized in ribosomes, then bent into their proper shapes. Simply, properly-activated sigma-1 receptor proteins modulate, facilitate proper enzyme structures. With that, waste-clearing enzymes are active and waste proteins cannot accumulate and cause the symptoms of Alzheimer’s. Similar processes are involved in Parkinson’s.

Propitious activation of the sigma-1 receptor facilitates a diversity of other good cellular functions, too lengthy to describe here. But in each of these outcomes, uniquely, they are controlled upstream, at the start of reaction sequences or pathways, thereby making “downstream” functions work. This is exactly why the Anavex molecules are so effective. Instead of trying to fix already broken things happening “downstream” within the neuron, they fix wrong things at their start, at the upstream, top, or start of reaction cascades or processes.

To certain degrees, this also works with genetic anomalies present at birth, such as the horrible symptoms of Rett syndrome.

As the story of the Anavex molecules begins rapidly to become recognized and depicted, notice the universal involvement of the Anavex drug’s activation of the sigma-1 receptor protein. That’s where the remarkably phenomenal therapeutic results will emanate from. Propitious activation of the sigma-1 receptor protein is the Anavex story. This year and next, with the completion of the on-going clinical trials (Rett syndrome, Parkinson’s disease dementia, and Alzheimer’s) the world will learn of — and benefit from — the company’s unique, proprietary science.