Anavex Life Sciences Corp (AVXL)

[MycroftHolmes]

Re: SIGMAR1 as a Genetic Biomarker

In the upcoming conferences, I will be listening with keen interest for any information on genetic biomarkers, in specific as it relates to the SIGMAR1 gene itself.

The SIGMAR1 is the gene which encodes the human Sigma-1 receptor. There are polymorphisms of the gene that are known flags for a variety of neurological pathologies. (ALS being the most well-known)

There have been studies which suggest that certain haplotypes have a protective role in AD and may even partially offset the high-risk ApoE4 gene itself.

There was a significant association between AD and the TT-241-240P2 haplotype of the SIGMAR1 gene and its homozygote, found with late-onset, but not early-onset AD. After stratification by e4 allele status of the apolipoprotein E gene, TT-241-240P2 homozygosity of the SIGMAR1 gene reduced the risk of AD in e4 allele carriers by three-fourths.

https://www.sciencedirect.com/science/article/pii/S1064748112619502?via%3Dihub

As half of the patients in the P2a trial had the ApoE4, I am curious to know if that was a factor in 2-73 response.

If ‘high-responder’ results correlate with presence/absence of ApoE4… coupled with a given SIGMAR1 haplotype… things start to get very interesting indeed.

Having a custom ligand for a specific Sigma-1 receptor polymorphic subgroup is about as precision medicine as it gets.

The science continues to intrigue.

Cheers,

Mycroft