Biotech Values

[biocqr]

GERN > Imetelstat Off-Target Mechanism Might Be Its Therapeutic Mechanism of Action

http://rnaitherapeutics.blogspot.com/

It should be added here that the Geron, ISIS, and Santaris chemistries are slightly different, but share the phosphorothioate modification which in my opinion is what is causing these toxicities.

Given that the half-lives of phosphorothioate oligonucleotides in the liver are about 1 month, one would expect the low-grade liver enzyme elevations to go away with time and they might not be a show-stopper for non-chronic applications of imetelstat.

That’s the somewhat good news.

The bad news: applying a phosphorothioate oligonucleotide-based telomerase inhibitor for the treatment of cancer and increases in platelet counts sounds like a bad joke. Thrombocytopenia (decreases in platelet counts) and anti-proliferative immunostimulation are well known side effects of large doses of phosphorothioate oligonucleotides. In light of that, claiming that imetelstat works via telomerase inhibition seems a bit optimistic to put it kindly.