Replies to post #475784 on Anavex Life Sciences Corp (AVXL)

[Investor2014]

This is the kind of subgroup analysis I have been posting about hoping to see after reviewing the PDD genetic analysis poster, although COL24A1 was not a gene specifically identified out of the 14,150 analysed.

A questions is then if the PDD trial whole blood transcriptomics didn't find the GWAS database COL24A1 gene had any note worthy effect in PDD, but perhaps that gene falls within the 30% non-overlapping gene pathways related to AD.

The result certainly looks promising based on the minimum context available just now.

[rx7171]

At what point does 65-75% slowing of AD progression merely become the expected rate of normal brain aging, just as a normal aging brain loses about 1% of mass per year?

[boi568]

Here's some amateur analysis of the new gene discovery on Stocktwits by Mayomobile and Peter Karol (posting as "Formeridiot88"):

Mayo:

Anavex’s GWAS (Gene data) is complete.
It was found that hundreds of genes were deferentially expressed before trial (pre-dose) and after 48 weeks (post-dose).

Most notably of these genes was COL24A1, a collagen gene which encodes portions of the extracellular matrix (ECM) formation. Collagen genes have been implicated in Alzheimer’s and are thought to have a role in neuronal maturation, circuit formation, axon guidance and synaptogenesis.

Of the 338 dosed patients, 240 of them had WT COL24A1, which was correlated to a significant bump in cognitive improvement compared to mutation patients.

ITT ADAS-COG: -2.0271
COL24A1 WT: -3.9011

With this in mind, a SIGNIFICANT number of patients only declined about 1.5 points from baseline. Healthy 75 year olds decline about 1 point in a year. This indicates that Anavex’s COL24A1 subgroup practically halted disease progression.

With this in mind, a SIGNIFICANT number of patients only declined about 1.5 points from baseline. Healthy 75 year olds decline about 1 point in a year. This indicates that Anavex’s COL24A1 subgroup practically halted disease progression.

Furthermore, CDR-SB was also improved in this subgroup.

ITT CDR-SB: -0.4831
COL24A1 CDR-SB: -0.9864.

Peter Karol:

I can explain meaning of the text. The Gene is involved in protein production, it is form of collagen from which the cellular matrix is build being a scaffold for ordering cells into tissues. Why is it important? Because it suggests that cognition gain is due to creation of new neurons that have find their place in the matrix. This phenomena is called neurogeneration. It seems Blarca coxes stem cells to decide and differentiate into neuron and the variant of the gene makes it easy for them to find their place in the matrix. This is different type of cognition gain than removal of plaque or over availability of neurotransmitters like donezepil . Very important.

It is entirely possible that some patients might gain brain volume not just lower the rate of loss. COL24A1 suggests that cognition gain is achieved through neurogeneration. In such case my mathematical model might have been true, predicting some to gain brain volume. Of course making something plausible does not make it true.

Regarding cognitive gain of patients with certain variant of COL24A1, the gene codes form of collagen used to make the extra cellular matrix. The tissues are organized by the matrix aggregate of cells. You have stem cells in your body on clue they differentiate into any type and migrate to the its matrix position. The GWAS suggests that the mode under which patients regain cognition is neuroregeneration that is from stem cells to new neurons to matrix regrowth of brain tissue. Quality of matrix helps here a lot.

So it is a different mechanism of cognition gain, donezepil thru oversupply of neurotransmitters, lequembi plaque removal and blarca thru neurogeneration