Wednesday, March 12, 2014
Imetelstat Off-Target Mechanism Might Be Its Therapeutic Mechanism of Action
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6 comments:
Thanks for the commentary. Considering one of the ET patients had been on the drug continuosly for almost 2 years without liver issues progressing be a pretty good sign?
Not actually Hy's Law given elevated ALP. That generally indicates some level of obstruction (cholestasis) rather than the massive liver damage indicated by Hy's Law.
Imatelstat was only tested in ET and PV to prove that it could be used in MF, MDS, AML, and Blast Phase MF. The 2 Trials on hold were about to end so is the FDA hold ment to make sure Geron collects this data to answer questions the FDA has. The trials that are not held are Tefferi's MF, Blast Phase MF, MDS,and AML as well as a Young patients with brain tumors trial.
Any reason that the lipid palmitoyl group, covalently conjugated to the oligonucleotide via a amino glycerol linker to "improves cell permeability in vivo" would not also be a potential issue? Possibly more then just the fact that it is a phosphorothioate oligo.
This is abstract on off target Imetelstat mechanism of action. This might explain the reversal of fibrosis. This was from the non small cell lung cancer trial. http://www.ncbi.nlm.nih.gov/pubmed/23545855
Seems like little anti-proliferative effect of imetelstat in the absence of p21 co-inhibition/absence. The intro also says that telomerase inhibition monotherapy unsuccessful so far, imetelstat notwithstanding.
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