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! And I am long $AVXL $ANVS $CRTX FYI
The Aduhelm fiasco brings about the realization that it certainly isn’t a A-beta the reason for the dementia of Azheimer’s. The press still touts its sister the tau tangles. This narrative now goes through trasformation into the story of neuroinflammation with which are bound the two above-listed companies $SAVA and $ANVS. The transformation is simple, both of them are connected witht the A-beta physiology as a gateway to the neuroinflammation narrative. $SAVA indirectly, through Filamin A (illustration below).
$ANVS by the way of binding to messengerRNA for the precursor protein APP for A-beta, and some other enzyme related to it. quote from Alzforum on posiphen.
Posiphen, also known as ANVS-401, is the pure (+) enantiomer of phenserine. Both compounds were originally developed by Torrey Pines Therapeutics and licensed to QR Pharma in 2008. Both Posiphen and phenserine reduce production of amyloid precursor protein by blocking translation of its mRNA. Phenserine also inhibits acetylcholinesterase, while Posiphen does not. It is dosed by mouth and enters the brain.
Posiphen acts on iron-response element sequences in the 5′ untranslated region of APP mRNA to inhibit protein synthesis. It reduced APP and Aβ in neuronal cultures and brains of wild-type and AD transgenic mice (Lahiri et al., 2007; Marutle et al., 2007). The drug was reported to be neuroprotective and neurotrophic in AD mouse models (Lilja et al., 2013; Lilja et al., 2013), and to normalize memory impairment, learning, and synaptic function (Teich et al., 2018).
Posiphen reportedly also blocks translation of α-synuclein mRNA, implying potential application in Parkinson’s disease (Rogers et al., 2011; Mikkilineni et al., 2012; Yu et al., 2013). The compound reduced α-synuclein expression in brain and gut, and improved intestinal function in the A53T α-synuclein transgenic mouse model of PD (Kuo et al., 2019).
By a whole battery of biomarkers these drugs lower the level of neuroinflammation. I have to confess that upon viewing video, where a physician has injected AD patients with approved anti-inflammation drug into the neck, in order to have it then flow into the brain to make then partially recover from cognitive decline, I was so impressed that I thought it was the end of the search for AD cure. Unfortunately, the physician has been stopped from doing it by FDA. But for reasons given below this is not the end of pursuing AD cure.
Now, the etiology wars come to decisive battle, so it seems. It is not yet clear in the press and the among the laymen but the battle order in this war comes to two choices: Neuroinflammation or Epigenetics. I wrote about the Epigenetics and chromatine remodeling. Link: https://piotrpeterblog.com/2021/03/05/novel-etiology-of-alzheimers-linked-to-neuronal-loss-of-function-due-to-changes-in-cellular-transcription-mechanism-and-dna-chromatin-complex-avxl-sava-atha-biib/ .
I stole an article posted by Amateur17 on iHub. Post #319819. Link: https://www.spectrumnews.org/news/autisms-link-to-chromatin-remodeling-explained/ . The aticle draws partly wrong conclusion as it suggests that CRISPR could help, whereas CRISPR is a method of gene editing and not fixing epigenetic chromatin remodeling. As I posted in the post  SIGMAR1 receptor agonist like cocaine alteres chromatin remodeling. Link to paper is inside post .
Nevertheless, I want to make certain predictions as new elements in this puzzle emerge. I think that neuroinflammation is just a symptom of neurodegenerative diseases. One fact is that, those who attack neuroinflammation do it indirectly and do not affect such wide spectrum of indications as $AVXL does, all by the virtue of addressing a symptom not a root cause. And even if it would be direct, it would be just only treating a symptom vs. wider systemic action (including chromatin remodeling) of Blarcamesine spread across many diseases. In this light the drugs which just temper neuroinflammation should produce immediate results with stagnation in the therapeutics effect with time, or even reversal. Blarcaesine should on the other hand produced slower and steady (to a point) recovery.
I will be watching the data from AAIC 2021 with that in mind. I am particularly interested in $SAVA’s data. If it shows any weakness I think this might bode poorly as well on $ANVS prospects, but only might.
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