Abstract
Tissue plasminogen activator (tPA) treatment is beneficial for patients with ischemic stroke when started within 4.5 h of stroke onset. However, the risk of intracerebral hemorrhagic transformation (HT) increases with the delay in treatment initiation. Development of vasoprotective drugs that attenuate HT after tPA treatment might improve the prognosis of stroke patients and extend the therapeutic time window of tPA. We identified vascular remodeling factors such as vascular endothelial growth factor (VEGF) and angiopoietin 1 as therapeutic target molecules for HT after tPA treatment. We demonstrated that HT was inhibited by intravenous administration of anti-VEGF neutralizing antibody/VEGF receptor antagonist or recombinant angiopoietin 1 in a rat thromboembolic model. After the animal studies, we acquired intellectual property rights and established an academic–industrial alliance. Presently, we aim to conduct a clinical trial to assess the effect of VEGF-inhibiting drugs on HT. From our experiences, to overcome “the valley of death”, which is the difficult period of transition from laboratory success to human clinical trials, in drug development, academic researchers need to focus on (i) improving the quality of animal studies, (ii) acquiring intellectual property rights, and (iii) promoting academic–industrial alliances.
