Replies to post #300955 on Anavex Life Sciences Corp (AVXL)

[georgejjl]

baltimorebullet,

My bet is Fragile X–Associated Tremor/Ataxia Syndrome | FXTAS

https://fragilex.org/understanding-fragile-x/tremor-ataxia-syndrome-fxtas/

Watch and listen to Dr. Randi J. Hagerman MD say that she wants to take Anavex 2-73 as soon as possible to prevent the issues caused by aging.

Watch starting at 38 minutes and 21 seconds and again at 1 hour and 16 for the Q & A including many questions and answers regarding Anavex 2-73

https://health.ucdavlis.edu/mindinstitute/videos/images/dls/hagerman-2021-dls.pdf

Good luck and GOD bless,

[falconer66a]

Blarcamesine facilitation of chromatin function probably favorable.

Any thoughts on the undisclosed rare disease in our pipeline? [Fragile X Syndrome]

I know the essential rudiments of cellular biology, particularly in normally functioning cells. But I had to read about the biochemistry, biochemical etiology of Fragile X Syndrome, to see how an Anavex sigma-1 receptor agonist might be therapeutic.

The syndrome is genetic. "The FMR1 gene usually makes a protein called fragile X mental retardation protein (FMRP). FMRP is needed for normal brain development. People who have FXS [fragile x syndrome] do not make this protein."
https://www.cdc.gov/ncbddd/fxs/facts.html

From this information it would appear that blarcamesine would be utterly non-therapeutic. The genetics of FXS patients lack the ability to code for or synthesize the essential fragile X mental retardation protein (FMRP). How, then, could blarcamesine work?

If the FMRP gene is missing altogether, blarcamesine cannot in any way "restore" it. Blarcamesine, for all of its wonderful functions, can do no genetic engineering. That's CRISPR technology.

Genes are long sequences of nucleotides, C's and G's, A's and T's, which must be in place in the DNA in chromosomes. The DNA in chromosomes is wrapped and enclosed in chromatin, which must be carefully "unwrapped" to allow messenger RNA (mRNA) to take the genetic message (hence the name) for the proper protein out to the ribosome where the proteins' amino acids are precisely sequenced. That makes a peptide, a fragment of a protein. Finally, the proper peptides are connected and folded, making (in most cases) a reaction-controlling enzyme. Control the reactions in a cell and then it spontaneously functions.

Now, it is clear that the Anavex researchers have strong information that blarcamesine will, somehow, prompt fragile-X to produce the missing protein, FMRP. Therefore, the gene for that must still be in the chromosomes, but it doesn't get expressed. The problem is not the lack of the gene. There's something inhibiting its expression. And, most likely, it's a dysfunction in chromatin modulation of the process for that particular gene. Evidence continues to accumulate showing that blarcamesine can, indeed, propitiously modulate chromatin function in gene expression.

Anavex wouldn't have placed Fragile-X Syndrome in the pipeline without preliminary, pre-clinical evidence that blarcamesine will be therapeutic. That was not a throw something at the conceptual wall and see if it sticks process.