Cellular and Molecular Metabolism
Our research is focused on identifying genes, proteins and pathways that are important in metabolic and inflammatory diseases, and then to develop pharmaceutical therapies that either activate or block the pathway of interest. We currently have three such candidates.
Together with N-Gene Pharmaceuticals, we have developed a drug (BGP-15) that has anti-inflammatory and anti-fibrotic properties. BGP-15 is currently in Phase 2B clinical trials for the treatment of type 2 diabetes, but has also shown efficacy in pre-clinical experiments for the treatment of Duchenne Muscular Dystrophy and Heart Failure, principally due to its anti-fibrotic effects.
Almost a decade ago, work from our lab showed that cytokines from the gp130 family of cytokines (IL-6 and CNTF) can protect against obesity and insulin resistance by activation of the fuel sensing kinase, AMPK. With our collaborator Professor Stefan Rose John at the University of Kiel, this led to the development of IC7, a designer cytokine which is a chimera of CNTF and IL-6. IC7 is showing promise as a drug to treat obesity and type 2 diabetes and we have recently commenced pre-clinical development. We hope to start first in human trials within 24 months.
Finally, together with the University of Kiel, we recently showed that a drug that can block IL-6 “trans-signalling” (sgp130Fc) can markedly prevent inflammation. Phase 1 human clinical trials for sgp130Fc have recently been completed and we are now focusing on the role of sgp130Fc for the treatment of Rheumatoid Arthritis, non alcoholic steatohepatitis (NASH) and other diseases where inflammation and fibrosis are major mediators.
Significant findings include:
- Identification that muscle is an endocrine organ: IL-6 the prtotypical myokine
- Identification that activation of HSP72 can result in protection against insulin resistance
- Discovery that the mechanism of action of gp130 receptor ligands CNTF and IL-6 in protecting against obesity and insulin resistance is via the activation of skeletal muscle AMPK
- The chemical chaperon BGP-15 can improve the pathology and functional capacity of skeletal muscle in muscular dystrophy and cardiac muscle in heart failure
- Blocking IL-6 transignalling can prevent high fat diet-induced inflammation