Edvince's drug discovery and development is born out of founder and Professor Lars Edvinsson's extensive, fundamental and pioneering research of blood circulation in the brain. Professor Edvinsson is a world leading neuroscientist in the field of cerebral circulation, receptor regulation, stroke and migraines. He has spent more than 40 years researching the blood vessels of the brain. In more than 950 scientific publications, he has described groundbreaking research that, among other results, has led to superior new drugs for migraine.
A novel transcriptional event was discovered, triggered by loss of blood flow and pressure in the vessel walls by activating the key mechanism Raf-MEK-ERK pathway, which later turned out to become a decisive discovery in the stroke field. In the years to come, this pathway was extensively explored, new stroke models were developed and potent inhibitors of the discovered pathway were identified. One of the most promising molecules turned out to be EDV2209, a potent and selective inhibitor of MEK 1/2 kinase. The groundbreaking discoveries in the mid-1990sth laid the ground for an extensive and successful research program in stroke, which took off in 2001 and is still ongoing at Professor Edvinsson’s sites in Lund and Copenhagen. His research team wanted to explore the relevance for the new mechanism and how it could potentially lead to a much-needed effective treatment of stroke. Professor Edvinsson decided to explore three directions: 1) transient middle cerebral artery occlusion and the reperfusion, 2) subarachnoid hemorrhage (SAH) and 3) global cerebral ischemia.
They later found upregulation of endothelin ETA and ETB receptors, angiotensin AT1, 5-HT1B/1D and thromboxane A2 receptors in the cerebral vessel walls after either type of stroke. Parallel molecular biology studies revealed the basic underlying mechanism in depth. This work is ongoing and is a fundament for future stroke projects.
The recent work by Mimmi Rehnström et al 2020 in the journal BMC Genomics showed a direct comparison that they hit most of the important pathways. An important proteomic study was made by Parker et al 2015 in the Journal of Cerebral Blood Flow and Metabolism and demonstrated the key importance of the MEK1/2 pathway and illustrated the coupling from the brain vessel wall due to reduction in shear stress (flow and pressure in the vessel segment) to focal adhesion kinase (FAK) to ras-raf-MEK-ERK1/2 pathway and the enhanced expression of receptors. Studies of MEK blockade during the entire period revealed positive results independent of intracerebroventricular or intravenous/intraperitoneal administration. For clinical purposes, they decided to study different administration times after the stroke event and length of treatment, as well as following the therapy for up to 2 weeks. Positive outcome was also observed with MRI, rCBF, cell damage volume, neuroscores, mortality and other functions.
The high fluorescence after SAH indicates high expression of ETB and 5-HT1B. Administration of EDV2209 causes an intense reduction in fluorescence intensity to the levels of a healthy subject.