A new method to link two hormones into a single molecule producing a more effective and safe therapy for obesity and related medical conditions has been identified by scientists.

"We find that combining the hormones as a single molecule dramatically enhanced their efficacy and their safety," DiMarchi said. "The combination improves the ability to lower body weight and the ability to manage glucose, and it does so without showing the hallmark toxicities associated with estrogen." The researchers believe GLP-1 acts as a "medicinal chaperone," targeting estrogen to the hypothalamus and pancreas, which are involved with metabolic processes. The precise targeting reduces the likelihood that the estrogen will produce negative effects, such as cancer and stroke. Brian Finan, a former doctoral student in DiMarchi's lab, is the lead author of the paper,
"Targeted estrogen delivery reverses the metabolic syndrome." Co-authors include Bin Yang and Vasily Gelfanov, research scientists in the IU Bloomington Department of Chemistry, and DiMarchi. Finan is now a post-doctoral researcher at the Helmholtz Zentrum München in Germany, directed by Tschöp, who is DiMarchi's longtime collaborator and a corresponding co-author. Affiliations of the other 20 co-authors include the University of Cincinnati where, also led by Tschöp, many of the in vivo pharmacology and molecular mechanism studies were conducted; Northwestern University; and research laboratories in Germany and China. Associated with what health authorities are calling a global epidemic of obesity, the metabolic syndrome consists of obesity associated with other factors such as high blood pressure, high triglycerides, hyperglycemia and low HDL cholesterol. The International Diabetes Federation estimates that as much as 20 percent of the world's adult population has some form of the metabolic syndrome and that they are three times as likely to have a heart attack or stroke and five times as likely to develop adult-onset diabetes as people without the syndrome. DiMarchi said investigation continues in the optimization of the peptide-based hormone conjugates with an emphasis on determining the specific mechanism of biological action and identification of an optimal drug candidate suitable for human study. The combination of other peptides and nuclear hormones for targeting other medical conditions holds considerable promise and opportunity for future research.
Source-Eurekalert