2018 Volume 30 Issue 1 Pages 11-15
Development of vasoprotective drugs that attenuate hemorrhagic transformation (HT) after tissue plasminogen activator (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) as a therapeutic target molecule for HT after tPA treatment. We demonstrated that HT was inhibited by administration of anti-VEGF neutralizing antibody/VEGF receptor antagonist in a rat thromboembolic model. After the animal studies, we acquired intellectual property rights in Japan and United States, established an academic-industrial alliance, and examined the role of VEGF in HT using human samples. Our goal is to conduct a clinical trial to assess the effect of VEGF-inhibiting drugs on HT. In addition, we found that a growth factor progranulin could protect against acute focal cerebral ischemia by variety of mechanisms, which we call “brain protection”, including neuroprotection in part by inhibition of cytoplasmic redistribution of TDP-43, suppression of neuroinflammation via anti-inflammatory interleukin-10 in microglia, and attenuation of blood-brain barrier disruption via VEGF. We’d like to accelerate further researches towards the development of novel combination treatments with “brain protective” drugs and tPA or thrombectomy.
