Anavex Life Sciences Corp (AVXL)

[MycroftHolmes]

Re: SIGMAR1 as a Genetic Biomarker

Investor2014:
Interesting indeed.

The company seems to be saying that they have identified genetic biomarkers that will be applicable not just to AD, but also for the Rett and PD trials.

Do you believe that the SIGMAR1 gene in various combinations (like with/without APOE expression) is potentially a common predictor of response in any indication for A2-73?

If one assumes that AVXL has identified a genetic biomarker common across disease, it raises interesting possibilities.

First, note that a polymorphism is normal genetic variation within a population whereas a mutation is a rare genetic variation.

For instance, there is an ALS associated genetic mutation of SIGMAR1 (E102Q). The mutation mis-aligns hydrogen bonding on the Sigma R-1 backbone which results in a misfolded Sigma-1 protein. In this case, accumulation of mis-folded SR-1 proteins is what causes dysfunction.

In Alzheimer’s Disease, of interest are two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Q2P. There is some research to suggest that haplotypes GC241-240/ Q2 and TT241-240/ P2 (in conjunction with ApoE4) are meaningful.

Related Study
https://www.ncbi.nlm.nih.gov/pubmed/21605063?dopt=Abstract
Explanation of Haplotype
https://www.nature.com/scitable/definition/haplotype-haplotypes-142

In Parkinson’s disease, genetic mutations correlate with mitochondrial dysfunction and oxidative stress.

In Retts, genetic mutations also correlate with mitochondrial dysfunction and oxidative stress.

In MS, genetics have been tied to inflammation and other symptoms.

Other polymorphisms of the SIGMAR1 have been tied to FTLD, MND, MDD, Schizophrenia, and alcoholism.

So I will be looking very carefully at Anavex disclosures involving 2-73's impact on genetics caused inflammation, Ca+ imbalance, BDNF Levels & Mitochondrial dysfunction... because there is a raft of science that would put such findings perilously close to a quantified Mechanism of Action for 2-73.

Can't wait for the data.

Just my 2 cents...

Cheers

Mycroft