Type II diabetes is a global rising epidemic. It is a medical condition where the body is unable to use insulin to take in glucose into the cell for energy usage. Millions of people are affected by type II diabetes worldwide, and the numbers are predicted to double by 2030. Although there are existing medications for type II diabetes, such as Metformin and Januvia, there are currently no treatments that can stop or reverse the disease progression. Therefore, there are still many research efforts focusing on finding new therapies for type II diabetes.
A promising new target for type II diabetes treatment is a protein called ciliary neurotrophic factor (CNTF). It is mainly studied for its useful ability to stimulate nerve cells, but it has also been found to reduce obesity and improve glucose uptake into cells. It does so by binding to two other structures: a protein, glycoprotein 130 (gp130), and a receptor, leukemia inhibitory factor recept (LIFR). This tri-component complex is then able to increase the breaking down of fats, improving insulin sensitivity in the body and thus having the potential to treat type II diabetes. Previously, a modified version of human CNTF, Axokine, entered clinical trials for treating type II diabetes. Despite initial success with patients, the drug was discontinued because most patients developed antibodies against Axokine. Since Axokine was structurally similar to the CNTF, these antibodies are especially dangerous as they could also attack the beneficial CNTF in our body.
In a recent study by Findeisen et al., they decided to engineer a chimeric protein to solve this issue. They realized that gp130 also binds to another protein, interleukin 6 (IL-6). Therefore, they took the part of CNTF that binds to LIFR, and added them onto IL-6, creating a chimeric protein made up of IL-6 and CNTF, which they call IC7Fc. IC7Fc is then able to bind to both gp130 and LIFR, activating the desired downstream signaling (Figure 1).
Figure 1: Simplified diagram showing the design of the chimeric protein, IC7Fc.
The key difference between IC7Fc and Axokine is that IC7Fc is mainly made up of IL-6, which is a very abundant protein that circulates everywhere in the body, while Axokine is a slightly modified version of CNTF, which is a protein that mainly resides inside a cell and is not exposed to the rest of the body as much. While our immune system might be wary of Axokine since it has never seen CNTF floating around in the body, they are less likely to be wary of IC7Fc, erasing the threat of antibodies being developed.
They tested IC7Fc in mice and found it lowered the blood sugar level and restored insulin sensitivity to obese mice. There were no unwanted immune system responses to the treatment as well. The results in this study are encouraging, and the authors are also excited to push this new potential drug into clinical trials. Looking at the initial success of Axokine, there is hope that IC7Fc could go further and become a new biological therapy for type II diabetes.
Managing Correspondent: Wei Li
News Article: Designer type 2 diabetes drug comes with added benefits. Medical Xpress.
The best of both worlds: a designer molecule to combat type 2 diabetes. Innovations Report.
Original Article: Treatment of type 2 diabetes with the designer cytokine IC7Fc. Nature.
Image Credit: Stefan Rose-John/University of Kiel (Featured Image) and Wei Li (Figure 1).