Anavex Life Sciences Corp (AVXL)

[MayoMobile]

Offline Commentary with Kevindenver

Me: New study from Denmark identifies cellular autophagy failure as ultimate cause of Parkinson’s disease. When autophagy is inhibited, catastrophic failure begins within the cell and waste buildup is left in its wake. This 100% supports why Anavex was so profoundly successful in the PDD trial.

https://knowridge.com/.../scientists-find-the-major.../
https://www.nature.com/articles/s41380-021-01207-w

Me: Missling stated once that our PDD data was exceptionally surprising because benefits were seen across the board. He said that PDD patients are usually all in somewhat different stages with different symptoms which makes it really hard to treat which probably led to multiple PDD failures over the last 2 years. In this article, it states that 90-95% of PD is caused by autophagy failure and cell waste buildup. This explains why we have such good results. With 80-90% of the population having S1R (which promotes autophagy) and 90-95% of PD being caused by poor autophagic function, we can reasonably treat somewhere between 75-85% of PD patients. The 75-85% would see great effectiveness with the remaining still see some benefit as has been seen in our other trials.

Kevindenver: Mayomobile, thank you for your summation. So when the cells can't communicate properly autophagy (cell death and recycle) fails, waste proteins build up and a disease state results. However if communication is restored via the mitochondrial communication mechanism, autophagy resumes and that reverses the disease process.

Me: Exactly correct!

Me: It was helpful to read Anavex’s PR: https://www.anavex.com/anavex-life-sciences-reports-new.../

AND: https://www.hindawi.com/journals/omcl/2019/3809308/

To understand autophagic function, especially as it pertains to the mitochondria. (mitopaghy)

Kevindenver: So PDD, PD, and AD are now all scientifically linked to the autophagy function and S1R modulation restores that process. Sure sounds legit. How does 2-73 work in Rett and the rare diseases? That too is thought to be at the mitochondrial level to right? Does it have to do with cellular communication?

Me: *tries to remember Rett pathology* “The MECP2 gene provides instructions for making a protein called MeCP2. This protein helps regulate gene activity (expression) by modifying chromatin, the complex of DNA and protein that packages DNA into chromosomes. The MeCP2 protein is present in cells throughout the body, although it is particularly abundant in brain cells.

In the brain, the MeCP2 protein is important for the function of several types of cells, including nerve cells (neurons). The protein likely plays a role in maintaining connections (synapses) between neurons, where cell-to-cell communication occurs. Many of the genes that are known to be regulated by the MeCP2 protein play a role in normal brain function, particularly the maintenance of synapses.

Researchers believe that the MeCP2 protein may also be involved in processing molecules called messenger RNA (mRNA), which serve as genetic blueprints for making proteins. By cutting and rearranging mRNA molecules in different ways, the MeCP2 protein controls the production of different versions of certain proteins. This process is known as alternative splicing. In the brain, the alternative splicing of proteins is critical for normal communication between neurons and may also be necessary for the function of other types of brain cells.”

https://medlineplus.gov/genetics/gene/mecp2/

Kevindenver: So again a protein is the final "target", but the how 2-73 helps is a different mechanism at the chromatin level. That level has to do with "fixing" the instruction set provided by the MECP2 gene and that's correcting at the DNA, mRNA level?

Me: That is correct, and an image on slide 12 of the corporate presentation demonstrates that as well.

Kevindenver: Thanks, every so often I like to do a "Check for understanding" step, this helped.

Me: Me too! Thanks for reminding me of this, there are so many trials running I sometimes forget important facts.