GTC Biotherapeutics (fka GTCB)

[jessellivermore]

Re Sepsis finding

Overall a pretty good paper.. They use the term sepsis to probably mean Septic shock or DIC, or a combination of the two.

The paper is compatable with the pathophysiology supporting the use of AT3 in DIC. As we get into DIC treatment with AT3-Atryn, we are entering in new era in medicine in which we study mal function of systems (in this case the coag and the inflamatory) and attempt to regain control to return the systems to propper function. Both the inflam and the coag system employ cascades which we understand are the body's method of choice in situations where urgent local problems (bleeding and infection in this example) require actions (clotting, and inflamation) which if they became widespread would be extremely dangerous to the individual. The cascades have a front side, eg the clotting factors and a backside eg. AT3. AT3 serves to limit the spread of the action. If AT3 levels fall, the body is less able to prevent a generalised condition such as DIC from becoming worse.

In the cascade systems serine proteases seem to be the molecule of choice for mediators. AT3 is a blocker of serine proteases...hence its value as a regulator. Its effects on serine proteases (called proteases in this paper) seem fairly widespread, even inhibiting the release of TNF from monocytes seen in DIC. In this paper the lack of thrombin receptors or the blocking of them would have the same effect as removing thrombin, essentually what AT3 does.

As an aside... IMHO Apoptis will eventually be seen as cascade controlled system also (why wouldn't it be). Raising the likelyhood ATRYN could play a dominant role in the treatment of AMI and Stroke.