A Perspective on the study by O'Reilly et al.,
"How Serpins Are Shaping Up" by R.W. Carrell, in Science 17 Sep 1999, p 1861.
Interesting concluding paragraph:
...Importantly, as the authors ask, will these modified forms have clinical efficacy? The good news is that there should be no hindrance to human therapeutic trials for infusion of L-antithrombin, as such material has been used unwittingly in transfusion medicine for more than 10 years. At least one manufacturer of antithrombin concentrates has, in a final pasteurization step, been converting up to 40% of the antithrombin into latent and other L-forms. A controlled trial of transfusions of multigram quantities of these concentrates showed no adverse effects. Frustratingly, patients with malignancies were excluded from the trial!
The latent and locked L-forms and the cleaved form are the conformations referred to by O'Reilly in his paper as antiangiogenic AntiThrombin based on their observed activity. He produced the latent form for his experiments by heat treating antithrombin with a citrate. |
