Focus on EAS Innsbruck 2016: Introducing the faculty - Plenary speaker Daniel Gaudet
08 January 2016
A forward-looking scientific Programme to excite, inspire and inform!
The EAS 2016 Scientific Committee has created a programme featuring ground-breaking speakers in their respective fields. EAS 2016 Innsbruck welcomes a distinguished international faculty to share their forward-looking perspectives on the latest developments in basic research and clinical practice in atherosclerosis and cardiovascular disease. You can find details of the Plenary and Workshop sessions now on the Congress website, www.eas2016.kenes.com.
Abstract submission is now open. Submit your abstract by January 11, 2016 for the opportunity to present your findings at this prestigious international Congress.
Here, in a series of newsletters, we introduce members of the EAS 2016 Innsbruck faculty.
Plenary session 3, Wednesday, June 01, 2016: Future Therapeutic Challenges
Daniel Gaudet, Canada: Lessons learned from emerging therapies for severe hypertriglyceridaemia
Daniel Gaudet is Professor of Medicine at Université de Montréal, Canada. He founded the Université de Montréal Community Genomic Medicine Center, the Lipid Research Group, as well as the ECOGENE-21 research group. Dr. Gaudet is currently the scientific director of the Genome Quebec Biobank. His research interests focus on rare genetic lipid disorders and their associated impact on risk for cardiovascular disease, type 2 diabetes, pancreatitis and metabolic consequences to obesity. Dr. Gaudet was the recipient of the Genesis Genome Quebec Biotechnology of Tomorrow Award in 2012.
Severe hypertriglyceridaemia is associated with an increased lifelong risk of recurrent pancreatitis, usually severe and often associated with complications including pancreatic insufficiency, necrosis and abscess. Treatment options are limited, and often compromised by genetic defects and lifestyle risk factors, highlighting the need for new approaches.
Given that severe hypertriglyceridaemia often has a monogenic basis, the rarity of these conditions poses issues when investigating potential new therapies. Furthermore, the most clinically relevant endpoint, as well as the risk versus benefit of treatment, warrants consideration. For example, in clinical trials in patients with lipoprotein lipase deficiency, investigation of alipogene tiparvovec did appear to reduce triglycerides, although in most cases the effect was transient. Due to the lack of a placebo control, mandated for ethical and practical reasons, patients were followed before and after treatment for both primary (triglycerides) and secondary (incidence of pancreatitis) endpoints; the therapy was finally approved on the basis of reduced risk of pancreatitis.
Recent data indicate potential for ISIS 304801, a second-generation antisense therapy to apolipoprotein (apo) CIII, a key regulator of triglyceride-rich lipoprotein metabolism. Mendelian randomisation studies showing loss-of-function mutations in the APOC3 gene coding for apoCIII were associated with low levels of triglycerides, as well as a lower risk of cardiovascular disease, provided a rationale for this approach. In patients with familial chylomicronaemia, treatment resulted in dose-dependent reductions in triglycerides, either as monotherapy or as add-on to fibrate therapy. However, there was also a corresponding increase in plasma low-density lipoprotein cholesterol levels, although this was less pronounced when combined with fibrate therapy. While a promising therapy, evaluation of the long-term efficacy of this treatment in a larger number of patients is still needed. Insights from genome-wide association studies also suggest novel targets for transcriptional and post-transcriptional regulation of triglyceride-rich lipoprotein metabolism which may offer future potential.
Gaudet D, Alexander VJ, Baker BF, Brisson D, Tremblay K, Singleton W, Geary RS, Hughes SG, Viney NJ, Graham MJ, Crooke RM, Witztum JL, Brunzell JD, Kastelein JJ. Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia. N Engl J Med 2015;373:438-47.
Rosenson RS, Davidson MH, Hirsh BJ, Kathiresan S, Gaudet D. Genetics and causality of triglyceride-rich lipoproteins in atherosclerotic cardiovascular disease. J Am Coll Cardiol 2014;64:2525-40.
Gaudet D, Brisson D, Tremblay K, Alexander VJ, Singleton W, Hughes SG, Geary RS, Baker BF, Graham MJ, Crooke RM, Witztum JL. Targeting APOC3 in the familial chylomicronemia syndrome. N Engl J Med 2014;371:2200-6.