Translating novel clotting factor X function to treat thrombosis

We have discovered a novel function for the plasma protein product, clotting factor X (FX), and stabilized this new function, which is a clot-dissolving agent called Xai-K. While blood clotting is essential for life, too much clot results in heart disease and stroke. Thus, we are aiming to translate Xai-K into a therapeutic to restore the normal passage of blood and help save these patients’ lives. While the prevailing clot-dissolving drugs have helped many people, they are not perfect. The foremost problem is that these drugs may cause bleeding in the brain. Addressing this serious problem, we reported that FXai-K was as effective in animals as the predominant clot-dissolving therapeutic (tPA). Furthermore, measurements of brain bleeding risk indirectly measured outside the brain indicated that Xai-K was safer than tPA. In the current grant application, our goal is to replace Xai-K with a recombinant version to make it more attractive to develop as a pharmaceutical. We will also evaluate safety in animals by directly measuring bleeding in the brain. Advancing toward a new therapeutic, recombinant versions
of Xai-K have been generated with effective clot-busting activity in a test tube and the direct brain bleeding safety of Xai-K has been confirmed compared to current drugs.

PRYZDIAL, Ed

Canadian Blood Services

Intramural Research Grant Program

British Columbia

$369,052