THR-18 Product overview
Ischemic stroke, caused by a blood clot in the brain that deprives brain cells of vital oxygen and glucose, sets off a race against time to
limit brain damage and save the patient's life. Immediately after the onset of initial symptoms, such as numbness, confusion, dizziness,
severe headache with no known cause or difficulty speaking, seeing or walking, victims should be rushed to a specialized hospital
stroke center.
For over a decade, the drug tPA (tissue plasminogen activator) has been the only stroke-treatment drug available. It has saved the lives
of many stroke victims who were able to reach a hospital capable of treating them in time. However, tPA has major limitations as it can
cause dangerous hemorrhaging in the brain, may be neurotoxic and is effective only within three hours of the stroke symptoms’ initial
appearance.
THR-18, Thrombotech's first lead compound, is a peptide derived from Plasminogen Activator Inhibitor-1 (PAI-1). When co-administered
with tPA, THR-18 has been shown in a variety of animal studies to improve significantly both tPA’s efficacy and safety profile.
THR-18 was shown to dramatically reduced infarct size, brain swelling and edema, damage to neurons, and incidence of both
hemorrhaging and mortality in animals, as documented in the volume 9 2006 issue of Nature Neuroscience. The net result is an
unprecedented improvement in the efficacy and safety of stroke treatment.
THR-18 adds the advantage of reducing the risk of hemorrhage, which is considered the main side effect preventing the wider use of
tPA for stroke therapy.
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Figure 1:
Decreasing side effects –
Diminished bleeding into the
brain as a result of tPA
administration Intracranial
hemorrhage (ICH); Rat
thromboembolic model |
THR-18 remarkably reduces the harmful side effects of tPA in rat
thrombolytic models (Figure 1). In addition, these models established that
THR-18 can attenuate neurotoxicity induced by tPA, which activates
harmful excitatory pathways. It was also found that THR-18 prevents the
deleterious opening of the blood brain barrier following tPA administration,
which causes swelling of the brain and damage to the nerves.
In addition, animal results revealed significant improvement of clot
dissolution by tPA when administrated with THR-18. Clot dissolution
results in recanalization and renewed blood flow, which in turn allows
improved neurological performance in patients.
Moreover, our pre-clinical results demonstrate that THR-18 has the
potential to extend tPA’s therapeutic time window beyond the 3-hour
window, enabling the majority of embolic stroke patient to benefit from the
treatment (Figure 2).
Hence, THR-18 has the potential to save several million more lives
around the world each year. |
Figure 2:
tPA administered 4 hours after stroke did not reduce
stroke volume, while THR-18 co-administered with
tPA causes significant reduction in stroke volume; Rat
thromboembolic model |
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