PhD students participating in August Krogh seminars receive 0,2 ECTS per seminar
AKC / CWS mini symposium: The engineered designer cytokine IC7 protects against obesity-induced metabolic disease
August Krogh / CWS mini symposium
Professor Mark Febbraio
13:00-13:55: Professor Hadi Al-Hasani
13:55-14:25: Dr. Benjamin L. Parker, PhD
Short break
14:30-15:00: Dr. Adam Rose, PhD
15:00-15:55: Professor Mark Febbraio
16:00-17:00: Reception for all participants
The engineered designer cytokine IC7 protects against obesity-induced metabolic disease
v/ Professor PhD, Mark A Febbraio, NHMRC Senior Principal Research Fellow, Head of Division of Diabetes & Metabolism, Head, Cellular & Molecular Metabolism Laboratory, Garvan Institute of Medical Research,The Garvan Institute of Medical Research, Sydney Australia.
Abstract
The gp130 receptor cytokines interleukin-6 (IL-6) and ciliary neurotrophic factor (CNTF) can improve obesity and insulin resistance in both mice and humans (Carey et al. Diabetes 55, 2688-2697, 2006; Watt et al. Nat Med 12, 541-548, 2006). However, due to the known inflammatory effects of IL6 and the antigenic response in some patients to the clinically used form of CNTF (Axokine), both proteins have limited, if any, therapeutic utility.
In an attempt to overcome this issue, we engineered a chimeric gp130 ligand, termed IC7, where one gp130 binding site has been removed from IL6 and replaced with the LIFR binding site from CNTF. This ‘module swap’ creates a new cytokine with CNTF-like, but IL-6R dependent activity. Here, we show that IC7 significantly improves glucose tolerance and hyperglycemia and prevents weight gain and liver steatosis in diet-induced obese mice.
In addition, we have shown efficacy and safety in non-human primates. In comprehensive human cell based assays, we show that IC7 treatment results in no signs of immunogenicity or inflammation. Thus, IC7 is a realistic and viable next generation biological for the treatment of obesity and T2D, disorders that are currently pandemic.
Supported by the National Health & Medical Research Council of Australia.
Relevant papers
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Carey, A.L., et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55, 2688-2697 (2006).
Watt, M.J., et al. CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med 12, 541-548 (2006).
3. Whitham M, Febbraio MA. The ever expanding myokinome: discovery challenges and therapeutic implications. Nature Rev Drug Disc. 15, 719-729 (2016).
Research profile
Professor Mark Febbraio is a Senior Principal Research Fellow of the NHMRC and Head of the Division of Diabetes & Metabolism at The Garvan Institute of Medical Research in Sydney, Australia. He is also the Chief Scientific Officer of N-Gene Research Laboratories Inc., a USA based Biotechnology Company and is the Founder of the company Kinomedica.
His research is focussed on understanding cellular and molecular mechanisms associated obesity, inflammation, and related diseases such as type 2 diabetes and cancer and his research is geared towards developing novel drugs to treat such diseases. He has authored over 220 peer reviewed papers in leading journals and has over 20,000 career citations. He has won prizes at international, national and institutional levels. Professor Febbraio is also dedicated to health and fitness and continues to compete in multi-sport endurance events.
Time
19 May 2017
13:00-13:55: Professor Hadi Al-Hasani
13:55-14:25: PhD Benjamin L. Parker
Short break
14:30-15:00: PhD Adam Rose
15:00-15:55: Professor Mark Febbraio
16:00-17:00: Reception for all participants
Venue
Auditorium 1, August Krogh Building, Universitetsparken 13, DK-2100 Copenhagen
Registration
Participation is free, but please register here.
For PhD students
PhD students participating in August Krogh seminars receive 0,2 ECTS per seminar
Contact
Jonas Møller Kristensen, jmkristensen@nexs.ku.dk, mobile +45 6092 1309