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 CGRP-inhibitors for migraine. He has written the major textbook in the field: Cerebral Blood Flow & Metabolism (1993 Raven Press, and 2002 Lippincott Williams Wilkins). In the field of headache, he is now the immediate past-president of The International Headache Society. In 2021, he was awarded the World ́s largest brain research prize, the prestigious Lundbeck Brain Prize in neuroscience, for his fundamental discoveries leading to the new generation of successful CGRP antagonist drugs for migraine.
Professor Edvinsson’s groundbreaking research on the sensory system has resulted in new CGRP migraine medicines being introduced by companies such as AMGEN, Novartis, TEVA, Eli Lilly, AbbVie (Allergan) and Lundbeck.
Professor Edvinsson’s research in stroke took a new and important direction in the mid-1990s when he examined the contractile response of endothelin ET-1 on guinea-pig basilar artery with the first novel and selective ETA receptor antagonist. He tested this blocker in several peripheral vascular models. 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-1990s 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.
A collaborating team at BMC had developed a model of cerebral artery occlusion. The rat models turned out to be a key element in the evaluation of the new mechanism and for the identification of therapeutically relevant molecules. With these two methods ongoing in parallel, they 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.
For several years the group examined proteomics and genomics in human autopsy material and rat tissues (the latter from the different stroke models including male and female). The recent work by Mimmi Rehnström et al 2020 in BMC Genomics showed a direct comparison that they hit most of the important pathways. Similar studies along this track were published in major scientific journals. The 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. The details of the role of the vessel wall shear stress were explored. 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 more than 25 years of pioneering research and breakthrough discoveries led by Professor Edvinsson has created a novel understanding of the brain blood circulation after stroke and how blood circulation can be restored to prevent ischemia and cell death which are the causes for mortality and brain damage of stroke patients.
Professor Lars Edvinsson and his co-workers have over the past decades published more than 300 scientific articles and 70 PhD thesis related to stroke. His research in the stroke field has been supported by public and private funds of approximately 350 MSEK from the Lundbeck Foundation, Swedish Research Council (Vetenskapsrådet), the Heart-Lung foundation, the KA Wallenberg foundation and by local founds like ALF and SUS foundations. Recently, Professor Lars Edvinsson was awarded the prestigious Brain Prize from the Lundbeck Foundation.