GTC Biotherapeutics (fka GTCB)

[MTB]

Hi Jessie,

I tend to believe your hypothesis that falling AT3 levels in sepsis are more than an artifact, and that where there is thrombin, antithrombin is likely to be present and biologically active. Our lymphatic systems didn't evolve with the feeding habits of common leeches in mind . . . while hirudin might have good experimental effect, I'd be surprised if the primary indigenous protein (ATIII) to mediate thrombin doesn't have good biologic effect in sepsis.

While thoracic duct interventions might help decrease the flow of inflammatory mediators into the central blood stream, they are modestly invasive (that old do no harm thing:). Hopefully, ATIII supplementation, even if it only has effect INTRAvascularly, will be sufficient to have good clinical effect on those inflammatory mediations.

What would be nice, is to have Dr. Ruf et al to run a couple of sets of their sepsis model using ATIII rather than hirudin. I'd be fascinated in the results, and would think it likely to have good effect. I'd think it would be in LEO's economic interest to slip him a few bucks to run these tests to shore up their pretest probability of finding good clinical effect.

Picked up someone's shares for 70cents at the close yesterday. Many thanks,

MTB