Anavex Life Sciences Corp (AVXL)

[MayoMobile]

Indeed, during the 2a, APOE status was a driving factor of therapeutic effect size.

“This analysis showed that the higher blarcamesine (ANAVEX2-73) mean concentration arm had improved therapeutic responses of 78% and 88% in adjusted MMSE and adjusted ADCS-ADL, respectively, relative to the low/medium arm at 148 weeks (P-values < .0008 and <.0001, respectively). In addition to time, APOE e4 status (P < .0001), and blarcamesine (ANAVEX2-73) mean concentration were significant predictors (Figure 2a and 2b and Supplementary Tables 4b, 4c).”

In fact, it was the only genomic factor that really differentiated the best performing group (improve over baseline), and the second/most performing group (dramatic slowing).

It would appear that APOE4 alleles cause extra dysfunction in the insulin & diabetic pathways (near the bottom of image 3). It seems this extra stress has a marked effect on mitochondria metabolism. Both of the articles below are attractive sources contributing to the focus on mitochondrial function.

It is my opinion that if caught early enough in progression, even an APOE4 patient would have good odds at improving over baseline, because it seems that protection of the mitochondria (as proven in Blarcamesine) prevents insulin resistance. It’s a bit of a continuous loop which can be broken by protecting mitochondrial homeostasis.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994704/#abstract-1title

https://www.ahajournals.org/doi/10.1161/circresaha.107.165472