TS01, a novel therapeutic regimen mimicking the natural, human thrombolytic system.
TS01 is composed of low, fractional doses of tPA and mproUK, an improved version of prourokinase.
Envisioned benefits of TS01
- Highly effective and efficient thrombolysis
- Significantly lower bleeding risk, fewer patients excluded from treatment
- Treatment initiation without delay, reaching underserved communities
The tPA/prourokinase (proUK) thrombolytic mechanism was established in vitro, in animal studies, and has been validated in human by a clinical study in patients with heart attacks (the PATENT trial, 1995). At the time, patients were treated with a bolus of 5% of the standard tPA dose followed by 50% of the proUK dose. Restoration of blood flow was equivalent to full dose tPA (TIMI 2&3 ~ 70%) or full dose proUK, but was associated with significantly fewer hospital deaths (1%) and no stroke complications.
Development of mproUK
ProUK is an inactive compound, a proenzyme. proUK targets the occlusive clot exclusively, where it converts to its enzymatic form (urokinase or UK). However, at high enough pharmacological level, about 1000 times the natural concentration, proUK can convert to UK spontaneously in the blood, causing bleeding complications. This liability prevented the drug approval of proUK.
TSI’s founders, deeply involved in the development of proUK. Dr. Jian-ning Liu went on to design an improved version of proUK. This new thrombolytic, mproUK, was specifically devised to be significantly more stable than proUK while retaining its clot dissolving efficacy. In addition, Dr. Gurewich found that the enzymatic form, mUK, once leaving the dissolving clot surface, happens to be neutralized by plasma C1-inhibitor. This property, unique to mproUK and controlable, constitutes an additional safety benefit, a further protection from bleeding side effects.
Aside from this unique C1-inhibitor interaction, the mechanism of action of mproUK, including its important synergy with tPA, is identical to proUK.