Day 1 :
University Medical Centre Utrecht, Netherlands
Time : 10:05-10:45
Arie Franx has completed his MD from Free University in Amsterdam and PhD from the University of Utrecht. He is specialized in Obstetrics/Gynecology. He has attended leadership programs at INSEAD (Fontainebleau, France), Harvard Business School and Harvard School of Public Health (Boston, MA, USA). He is currently the Professor of Obstetrics and Director of the Ob/Gyn Specialty Training in the University Medical Centre Utrecht. His research interest includes pregnancy complications, cardiovascular health in women and organization and quality of care. He has published over 150 papers in international peer-reviewed scientific journals.
The aim of this presentation is to review the relationship of reproductive and pregnancy disorders with cardiovascular disease. Women who experience vascular-related complications in reproduction and pregnancy, such as polycystic ovary syndrome (PCOS), premature ovarian failure (POI), spontaneous preterm birth (SPB), pregnancy-induced hypertension (PIH) and preeclampsia (PE) have increased prevalence of traditional, modifiable cardiovascular disease (CVD) risk factors, including all the major defining criteria of the metabolic syndrome. Furthermore, epidemiological studies have demonstrated that women with PIH and PE are at two to eight fold increased risk of ischemic heart disease at (median) 14 years after pregnancy. Because of the relatively young age at which reproductive and pregnancy complications occur, absolute 10-year CVD risks are low at diagnosis and therefore most current guidelines on CVD risk management do not include recommendations on screening and preventive interventions in these women. Nevertheless, they may benefit from secondary CVD prevention on the long term. We have investigated the feasibility of screening and preventive intervention for CVD risk factors in these women, and also developed a national guideline for cardiovascular risk management in women with reproductive and pregnancy disorders. For a better understanding of the relationship of reproductive and pregnancy disorders with cardiovascular disease, including evidence-based preventative strategies, its pathophysiologic mechanisms need to be unravelled and longer-term follow-up studies are needed to evaluate the development or decline of cardiovascular health in these women in the course of life. Ultimately, cost-effectiveness of interventions to reduce CVD in these women needs to be evaluated in large-scale randomized studies.
SungKyunKwan University, South Korea
Time : 10:45-11:25
Kang Choon Lee is a Professor at College of Pharmacy, SungKyunKwan University, South Korea. He is internationally recognized as one of the leading Experts in site-specific peptide/protein pegylation and firstly demonstrated the therapeutic potential of novel site-specific pegylated drugs such as GLP-1. He has published over 150 papers in peer-reviewed journals and served as an invited speaker at many international conferences. He is honored as a Fellow of the American Association of Pharmaceutical Scientists in 2003.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone derived from the transcription product of proglucagon gene and normalizes blood glucose by activating the GLP-1 receptor. However, a major pharmacological problem with GLP-1 is its short half-life that is impractical as a therapeutic option for type 2 diabetes; thus necessary to develop long-acting GLP-1 receptor agonists. PEGylation is a commonly utilized technique to improve drug solubility and stability, prolong blood circulation time, reduce immunogenicity, and decrease dosing frequency. As with any form of molecular modification, the active site is affected and can drastically decrease the bioactivity of the therapeutic agent, especially when the modification is performed on a small molecular weight molecule like peptides, GLP-1. Steric hindrance from high molecular weight PEG can lead to a dramatic loss in the biological and pharmacological activity of the molecules. Therefore, it is generally accepted that a balance must be struck between the molecular weight of the PEG and the activity of the therapeutic molecule to reach sufficient drug efficacy. Unlike existing pegylation technology or other half-life extension technologies that often significantly reduce the biological activities of peptide drugs, we developed a new long-acting GLP-1 by utilizing a novel pegylation method with a very long half-life (88 h in non-human primates vs. 2 h exenatide) combined with retention of exenatide’s activity, resulting in a long duration of action with potentially reduced adverse effects in humans. This presentation focuses on the strategic pegylation of potent therapeutic peptides for GLP-1 and its potential applications.