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birinapant
Yes, they might just cover the preclinical research, in their hydrodynamic mouse model. But the announcement was written in a way that it claims that it works in the human system. Since by now they will have at least a few patients beyond the four weekly doses and the effect on hbsag should be quite immediate, they certainly must have human data by now. He might just present these in a last slide - or not.
Would it be able that you ask them more specifically if some preliminary data on the ongoing trial will be part of the discussion?
At any rate, thank you for the effort you already made.
The fundamental difference between all the inhibitory drugs to block the HBV system, which do not destroy the source but just limit the virion or accessory protein output while they are dosed and this approach is that it aims to eliminate the source of the infection itself cccDNA or integrated.
The mechanism operative is hoped to be that a not so effective immune signal tries to initiate apoptoses in infected cells. This is a scenario that we expect in chronic HBV, particularly in e negative, because the key cd8 epitopes are adapted and mutated, so the attack CTLs are too weak to push the cell into apoptosis with the signals provided.
However a key mechanism by which the cell avoids apoptosis under stress is the production of anti apoptotic proteins, that block milder apoptotic signaling. By introducing the SMAC/DIABLO mimetic birinapant, these antiapoptotic protectors are themselves inactivated, so now apoptosis happens.
The drug has been used in several human cancer trials, side effects seem to be very mild, the worst being Bells Palsy, reversible.
The mouse data are stunning, hbsag was lost in 4 weeks. But of course the model has its limits and the human situation can be quite different.
the biggest fear was or is that the effect is too strong and if a large percentage of liver cells are infected, acute fulminant hepatitis could result.
The plan apparently is to start with patients on antivirals which are UND and also to use a very small starting dose.
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发表于 2015-3-14 21:35
