Shane Wright. Credit: Johannes Frandsén.
Researchers at Karolinska Institutet have developed a novel method utilizing biosensors to predict adverse drug reaction risk. The method is targeted at obesity and type II diabetes drug formulations and can predict adverse reaction potential before the drugs are administered to patients.
"Our publication shows that drugs that bind GLP-1R—an important target for type II diabetes and obesity—change the shape of this receptor in different ways despite being developed to achieve the same outcome, said Shane C. Wright, a postdoctoral researcher at the Department of Physiology and Pharmacology, Karolinska Institutet. "Using biosensors, we show that these differences propagate throughout the cell, by changing the signaling proteins that interact with the drug-bound receptor and the subcellular compartment where this takes place (i.e., plasma membrane, endosomes, Golgi apparatus, endoplasmic reticulum).”
In the study, published in Nature Communications, the researchers compared the signaling location and profiles to adverse reactions reported to the FDA and discovered that a strong correlation exists between the reactions and the signaling profiles.
"These results are important because they may redefine the way that we explore the action of novel drugs and help guide our understanding of how to make new treatments with fewer side effects for patients,” said Wright. "This was an international, multidisciplinary study that debuted a new suite of biosensors that can measure signaling in living cells with subcellular resolution (15 pathways in 4 cellular compartments). Together with comparative structure analysis, time-lapse microscopy and phosphoproteomics, we thoroughly characterized a subset of anti-diabetic drugs used in the clinics as well as a newer drug in clinical trials that is available in tablet form.