Novel Therapeutic Concepts
In the research area “Novel Therapeutic Concepts”, the DZD is developing new approaches to therapy and treatment. Discoveries from basic research, such as innovative molecular targets or candidate molecules for new diabetes drugs are being developed further and transferred to clinical practice. The DZD experts are pursuing the following objectives:
DZD scientists are developing different synthetic hormone molecules, each combining the effect of two or three natural gut or pancreatic hormones. Thus, the researchers have succeeded in mimicking a surgical method for weight loss by means of less risky methods. A gastric bypass can be imitated by combining several hormones into a new active ingredient - a multihormone molecule.
A new active substance that combines the effects of the three gastrointestinal hormones GLP-1, GIP, and glucagon lowers blood glucose levels and reduces the body fat to a previously unknown extent. In the animal model, the triple hormone not only drastically lowers blood glucose levels, reduces appetite and body fat, but also improves fatty liver, cholesterol and calorie burning more effectively than previously available mono-acting or dual-acting molecules. The tri-agonist reduced body weight by about 30 percent.
In order to better treat the fatty liver in the future, DZD researchers have engineered chemical conjugates of the thyroid hormone T3 and glucagon, enabling targeted delivery into liver cells in order to stimulate the metabolism there. The new active substance does not infiltrate tissues without glucagon receptors. Thus, adverse effects on cardiac function and bone integrity are avoided.
Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease. Cell , doi: 10.1016/j.cell.2016.09.014
Hypothalamic leptin action is mediated by histone deacetylase 5. • Nature Communications 7, Article number: 10782 (2016), doi:10.1038/ncomms10782
Control of diabetic hyperglycaemia and insulin resistance through TSC22D4. Nature Communications 7, Article number: 13267 (2016) doi:10.1038/ncomms13267
Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability. Cell 2016 Aug 11;166(4):867-80. doi:10.1016/j.cell.2016.07.028
AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue. Cell Volume 165, Issue 1, p125–138, 24 March 2016, doi: http://dx.doi.org/10.1016/j.cell.2016.02.044
Dr. Timo Müller
Institute for Diabetes and Obesity