TSI Treatment Regimen
The synergistic effect of the tPA/HisproUK dual regimen is similar to starting and driving an automobile. Just as a car cannot run without both a starter and gasoline, tPA starts the natural process of thrombolysis by activating plasminogen and creating two additional plasminogen-binding sites. HisproUK then activates these binding sites, a step that accelerates thrombolysis – much like hitting the gas pedal of a car. Together, these synergistic mechanisms drive the process of clot dissolution.
How it Works
Hear about sequential lysis in
Prof. Victor Gurewich’s presentation
of TSI’s thrombolytic solution.
Blood that flows through arteries, veins and capillaries is considered “whole blood”: approximately 55% plasma and 45% blood cells, ie: white, red, and platelets. A blood clot is aggregated platelets and red blood cells that form a plug, in a mesh of cross-linked fibrin protein. A clot can be a healthy response to injury intended to prevent bleeding (then called a hemostatic plug), but can also be harmful when the clot obstructs blood flow through healthy arteries or blood vessels.
Compare TSI's Treatment Regimen to the Current Model
The tPA/proUK thrombolytic mechanism was established in vitro and in animal studies, and validated in post-MI patients in the PATENT trial. In that trial, restoration of blood flow was equivalent to almost double that of full-dose tPA, but was associated with six times (6x) fewer hospital deaths and no stroke complications.
tPA's biological role is limited to degrading the surface of the clot. With TSI’s regimen, once this occurs, the small amount of tPA used is then rapidly cleared from the blood flow. HisproUK exclusively targets the degraded clot and dissolves it, and is then also rapidly cleared from the blood flow. Should there be no degraded clot, either after a clot has been fully dissolved, or in the case of stroke mimics or a hemorrhagic stroke, HisproUK will remain in its inactive pro-enzymatic form and will itself safely be cleared from the blood flow. TSI's thrombolytic regimen could therefore be given safely on simple suspicion of an ischemic stroke, as soon as possible after stroke onset.
In a patient with MI, TSI’s combination regimen can be used instead of or in addition to angioplasty, depending on whether the patient can get to a catheter lab and/or withstand the procedure. As an add-on to angioplasty, the HisproUK/tPA combination can improve reperfusion and reduce the risk of a future event.
A recently completed Phase 1 clinical study in 26 healthy volunteers confirmed the safety and tolerability of the tPA/HisproUK dual regimen.
TSI is working with two world-renowned European medical research centers to design two Phase II confirmatory studies – one in stroke patients, the other in MI patients. These studies will aim to replicate previous successful studies of proUK, but using the improved proUK mutant HisproUK. These initial studies will test TSI’s dual treatment regimen versus high dose tPA monotherapy, and therefore will need to be administered in a hospital setting.