by Researchers from the Karolinska Institutet have developed a groundbreaking method to predict the risk of adverse drug reactions in novel treatments for obesity and type II diabetes. The study, published in Nature Communications, highlights the importance of studying signaling within cells to determine the potential side effects of new drugs before they are administered to patients.
The team, led by postdoctoral researcher Shane C. Wright, focused on drugs that target the GLP-1R receptor, which plays a crucial role in the treatment of type II diabetes and obesity. Despite having the same objective, the drugs were found to alter the shape of the receptor in different ways.
Using biosensors, the researchers observed that these variations in the receptor’s shape resulted in changes throughout the cell, affecting the signaling proteins and the cellular compartments where the interactions occur, such as the plasma membrane, endosomes, Golgi apparatus, and endoplasmic reticulum.
Through a comparison of the signaling profiles and locations of these drug-induced activities, which they refer to as “signaling neighborhoods,” the team discovered a correlation with adverse drug reactions reported to the U.S. Food and Drug Administration (FDA).
The significance of this finding lies in its potential to revolutionize drug development by providing a new insight into the mechanisms of action of novel drugs. By understanding how drugs interact with the body at a cellular level, researchers can develop treatments with fewer side effects.
The study involved a multidisciplinary team and introduced a suite of biosensors capable of measuring cellular signaling with subcellular resolution. The researchers employed various techniques, including comparative structure analysis, time-lapse microscopy, and phosphoproteomics, to analyze a subset of anti-diabetic drugs used in clinical practice. They also investigated a newer drug, currently in clinical trials and available in tablet form.
Building upon these findings, the team plans to expand their research to include a wider range of drugs and disease targets. This will enable them to better predict the risk of adverse drug reactions before the drugs are administered to patients.
This innovative approach towards predicting adverse drug events has the potential to revolutionize drug development, allowing for safer and more effective treatments for patients suffering from obesity and type II diabetes.
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1. Source: Coherent Market Insights, Public sources, Desk research
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