Do not trade this blog as 4 billion years of evolution is against me and possibly even God laughs at it, He has a great sense of humor!
Another Paper Supports Anavex’s SIGMAR1 Platform
Just a day before Anavex published release with reference to a paper looking into Alzheimer’s patients brain geograghy of mitochodrial dysfunction, synaptic density, oxidative stress and their impact on brain volume. All this was done in vivo that is on living AD patients as novel radiograghic markers to measure these in PET scans became available. Imagine, you have a AD patient, you inject him with this marker, then put him into PET scan machine and get image of his brain with location and density of that marker in his brain as the marker binds to specific enzymes or proteins connect to given physiological function.
The Papers Approach To Alzheimer’s Does Not Focus On The Plaque
I would even add that the approach actually dismisses the plaque and focuses on measuring the occurance of mitochondrial dysfunction, oxidative stresss, synaptic loss and the degree of cell stress. It is surprising to find that among the authors were scientists from Biogen, AbbVie, Pfizer, Takeda and Bristol Myers Squibb. This would mark a determined departure from the plaque theory. Nevertheless, the most important aspect of the paper is that for the proxy of cellular stress SIGMAR1 receptor expression has been selected, and it was present in all the AD patients. They are using SIGMAR1 receptor as indicator, and not to purpose it as therapeutic target. The discussion of inquiry into SIGMAR1 expression among Alzheimer’s patients and the placebo group is the most interesting to investors in Anavex. Namely, the paper beyond using SIGMAR1 presence on the brain cells makes suggestions of great importance to the expected therapeutic effect of Blarcamesine.
- Alzheimer’s is associated with cell stress which in turn leads to greater expression of SIGMAR1 receptor on the stressed cells.
- Brain has redundency in its capacity for plasticity. Onset of cell stress preceeds any symptoms of dementia or cognitive decline. Yet, with cell stress SIGMAR1 is strongly expressed even long before symptons of cognitive decline.
- The paper suggests that previous studies which measured SIGMAR1 expression in more advanced Alzheimer’s patients were flawed by not accounting for Donezepil strong binding to SIGMAR1 receptor so that the marker could not bind to it and mark the SIGMAR1 occurance. In other words SIGMAR1 expression is strong even in more advanced patients but their brains are already devastated by the disease.
If SIGMAR1 Is A Valid Therapeutic Target Then Expect Great Things From Blarcamesine In Phase 2b/3
From evolutionary point of view the expression of SIGMAR1 in Alzheimer’s has to serve some function, or at least it did. In the results from phase 2a AD and PDD Phase 2 it is obvious that there is strong therapeutic effect. The paper does not make this connection, it just uses SIGMAR1 to validate the point that cell stress is present in AD brains, and that identity can be made between Alzheimer’s and SIGMAR1 elevated expression. This strengthens the ANAVEX’s claim to expect oversized therapeutic effect in Phase 2b/3 AD. If the first sign of cell stress is SIGMAR1 expression preceeding any symptoms and agoinists like Blarcamesine can set in motion processes leading to restoring homeostasis then Blarcamsine can become the Pill Before Dementia.
With the increased expression of SIGMAR1 Blarcamesine increases its therapeutic efficacy. Connecting AD to increased expression of SIGMAR1 means Blarcamesine is the drug.
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