Developing novel chimeric cytokine proteins for the treatment of metabolic disease

Type 2 diabetes (T2D) is highly prevalent, with an estimated 370 million affected individuals worldwide, and this is predicted to double by 2030. Despite the presence of several well-established drug classes for treating T2D, there is still a considerable unmet need for a drug that halts or reverses disease progression. Previous work from our laboratory demonstrated that the gp130 receptor cytokines interleukin-6 (IL-6) and ciliary neurotrophic factor (CNTF) can improve metabolic disease, but due to the known pro-inflammatory effects of IL-6 and the antigenic response to the clinically used form of CNTF (AxokineTM), both proteins were shown to have limited therapeutic utility for treatment of type 2 diabetes (T2D). Accordingly, we are engineering novel chimeric gp130 ligands to treat metabolic disease. We have shown that some of these new proteins significantly improve glucose tolerance and hyperglycaemia and prevent weight gain and liver steatosis in both obese mice and in non-human primates. We hope to develop a realistic next-generation biological for the treatment of obesity, T2D, and age-associated sarcopenia, disorders that are currently pandemic. This project will specifically look at testing newly synthesised compounds as potential biological treatments for T2D.