GTC Biotherapeutics (fka GTCB)

[jessellivermore]

Re DIC and Atryn

The rationale and promise comes from the Kyber-Sept study of DIC patients. Sorry if you want numbers you will have to check them out yourself (its sunday morning ) Basically DIC (disseminated intravascular coagulation) is a very serious and frequently fatal sequale of septcis. In DIC a hyperthombotic condition results in depletion of the platelets and coagulation elements leading eventually to bleeding. This condition has been recognised since the sixties when it was suggested despite the eventual bleeding problems that heparin might be useful. Heparin blocks the cascade and does improve survival somewhat.

In the KS study patients were treated with heparin, and heparin with AT3. It was known that AT3 levels are depressed in DIC. The study showed AT3 heparin treated group showed no increased survival over heparin alone. This seemed to cast some doubt on the importance of AT3 in the treatment of DIC. On closer inspection however there was a small but sigificant "subset" of patients who were treated with AT3 and no heparin. This set of patients did show a significant increase in survival over the Heparin or the AT3-Heparin groups. How could that be??? Well AT3 is an enzyme (a serine protease inhibitor) Like all this type enzyme it has as well as an active end, a glycolised end which effects the activity of enzyme (sorry this is confusing,,the specificity of the active end is not changed, the enzyme itself just becomes more or less efficient at doing its job). Heparin is a polysaccaride (sugar based) and decreases the over efficiency of AT3 by effecting the glycolisation.

This subset data is extremely compelling. In this case the doctors were looking survival improvement by adding AT3 to Heparin. The fact they were willing to accept the fact AT3 was ineffective in this setting is important because it clearly shows a lack of bias. They were no doubt unaware of the effect of heparin on AT3. The serendipitous recognition of this signifant subset is a compelling arguement for the effectiveness of Atryn without Heparin for the treatment of DIC.