Replies to post #9777 on GTC Biotherapeutics (fka GTCB)

[jessellivermore]

Keitern......

Very good .....you got it

[gym gravity]

one of the amazing things about something like ATryn is that it is a molecule that makes a chemical transition from a three dimensional kinetics (floating in plasma) to a two dimensional kinetics(binding to a region of endothelium via glycoproteins). I have to get out my old chemistry texts.

[MTB]

Hi Keitern,

You understand much more than you give yourself credit for. I'm sorry if I didn't do a good job explaining that second point.

On the point of ATIII's anti-inflammatory effects, in the Weidermann paper, I found Figures 2 and 3 to be helpful and informative schematics -- certainly more so than my prose -- in explaining the anti-inflammatory effects of ATIII.

At first, I found the nomenclature of "'HSPG'/ATIII binding" to be somewhat confusing.

While the HSPG structures (extending from the cell membranes of white blood cells and the cells lining blood vessels) are 'heparin like,' that description ONLY pertains to their molecular structure -- NOT to their effect. They have nothing to do with the anti-clotting effects (regulated through thrombin) of ATIII.

So while they share structural similarities to heparin, HSPG's are bound to cells and have a completely different role/ effect -- of decreasing inflammation. When HSPG's on cells are bound by ATIII, they have anti-inflammatory effects by decreasing the release of inflammatory mediators/ inflammatory response by that cell.

The only (significant for us) manner that heparin and HSPG's (and so anti-inflammatory effect) interact, is that any exogenous heparin administered disrupts ATIII's ability to bind the HSPG's, and so disrupts ATIII's anti-inflammatory effect.

I hope this is a little helpful. Figures 2 and 3 are likely to be more so :)

I appreciate the chance to try to make more clear, my prior post.

Best Regards,
MTB