The Health Prize of the Interbrew-Baillet Latour Fund, worth nearly $200,000, is the most prestigious international scientific prize awarded in Belgium. On May 12, 2005, Desire Collen of the Flanders Interuniversity Institute for Biotechnology and Peter Carmeliet of the University of Leuven will be honored with this award for their pioneering work in genetics and cardiovascular disease. The JCI spoke with the scientists about the prize and the work leading up to it. JCI: How were you selected for this prize? Carmeliet: An international jury of renowned scientists selected the laureates among 21 candidates from 13 different countries. JCI: What aspect of your work directly contributed to your winning this prize? Collen: I started my scientific career studying the molecular mechanisms of blood clot dissolution. These studies ultimately resulted in the isolation and characterization of tissue-type plasminogen activator (tPA), which digests blood clots. This led to the development, with Genentech Inc., of recombinant tPA for the treatment of acute myocardial infarction. Carmeliet: In the early 90s, I teamed up with Desire Collen to study cardiovascular diseases using gene targeting and focused on the molecular basis of angiogenesis in health and disease. These studies elucidated the role of angiogenic factors, in particular of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), and tested novel strategies to treat cancer, inflammation, and ischemic tissue disease. Recently, our team provided evidence for the therapeutic potential of VEGF for the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). JCI: What are the most direct clinical consequences of your work? Collen: The discovery of tPA and its development as a novel thrombolytic drug has saved the lives of a few percent of the more than 5 million treated patients with myocardial ischemia worldwide. Carmeliet: Mice deficient in a single VEGF allele revealed the key role of VEGF in angiogenesis. Further studies demonstrated that PlGF, a homolog of VEGF, affects angiogenesis in disease but not in health. The implication of these findings is that blocking PlGF might combine efficacy in inhibiting tumor growth with safety of only affecting tumor but not quiescent vessels. Conversely, delivery of PlGF stimulated revascularization of ischemic tissues. Our studies also showed that low levels of VEGF cause motor neuron degeneration, reminiscent of ALS. We have now demonstrated that VEGF prolongs survival in ALS rodent models. Clinical trials are underway. JCI: What is the biggest challenge you face? Collen: To secure a steady flow of funding and talented researchers to compete at the front line of basic research and to efficiently transfer technology for potential medical applications to interested industrial partners. Carmeliet: Understanding the molecular basis of angio-genesis and lymphangiogenesis, using mouse, zebrafish, and frog genetic models. Our focus is evolving from identifying which signals stimulate endothelial cells to migrate and divide, to understanding how blood vessels, lymph vessels, and neurons navigate to their targets. Our discovery that VEGF has neurotrophic effects in animal models of ALS may indicate a new approach to treatment of this and other life-threatening neurodegenerative disorders. A challenge will be to initiate clinical trials, evaluating the therapeutic potential of VEGF for ALS. JCI: In a typical day, how much of your time do you spend in the lab involved in research? Collen: I am primarily involved in the overall coordination of the research programs of approximately 160 investigators and technical staff. Much of my time is devoted to drug development programs spun out of the laboratory into dedicated spin-offs. I primarily focus on drug development and technology transfer issues. Carmeliet: Apart from some teaching and administrative duties, I, together with 4 other senior associates, spend my entire time supervising and coaching a research team of 55 postdocs, PhD students, and technicians. I am primarily involved in the conception of projects, writing grants and papers, and managing and coordinating the mouse, zebra-fish, and frog facilities. JCI: What do you think is the most important discovery you have ever made? Collen: The molecular regulation of physiological fibrinolysis (breaking down blood clots) and its application to fibrin-relative thrombolytic therapy of acute myocardial infarction. Carmeliet: Three discoveries seem most relevant: the critical role of VEGF in vascular development and disorders; the finding that PlGF is involved in angiogenesis in disease but not in health, and that PlGF stimulates revascularization of ischemic tissues, while PlGF blockers inhibit pathological angiogenesis; the finding that VEGF is a key survival factor for motor neurons in ALS and that VEGF prolongs survival of ALS rodents. JCI: What is your ultimate scientific goal? Collen and Carmeliet: Understanding the molecular mechanisms governing cardiovascular and nervous system function, and the development of mechanism-based novel treatments for life-threatening cardiovascular and neurological diseases.
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Feb 29, 2020
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