Scientists have introduced a groundbreaking computer model that promises to revolutionise drug development by shedding light on how medications impact men and women differently, ultimately leading to safer and more effective drugs.
It is well-documented that women often experience a disproportionate number of liver-related problems as a result of medication. Paradoxically, they are frequently underrepresented in clinical drug testing. In response to this disparity, University of Virginia Health (UVA Health) scientists have engineered intricate computer simulations of both male and female livers. These simulations are uncovering gender-specific distinctions in how drugs affect liver tissues.
This innovative model has already yielded unprecedented insights into the intricate biological processes occurring in the liver, the body’s primary detoxifying organ, for both sexes. Beyond its role in understanding liver function, this model serves as a potent instrument in drug development, aiming to ensure that new medications do not trigger harmful side effects.
Dr. Jason Papin, a UVA researcher and one of the creators of the model, explained, “There are incredibly complex networks of genes and proteins that control how cells respond to drugs. We knew that a computer model would be required to try to answer these important clinical questions, and we’re hopeful these models will continue to provide insights that can improve healthcare.”
Addressing the harmful effects of drugs is of paramount importance. Papin collaborated on the model’s development with Connor Moore, a PhD student, and Dr. Christopher Holstege, an emergency medicine physician at UVA Health and the director of UVA Health’s Blue Ridge Poison Center. Dr. Holstege stressed the significance of ensuring that both men and women receive the appropriate doses of recommended medications, emphasizing the complexity of drug therapy and the potential for toxicity with even slight dosage variations.
To lay the groundwork for their model, the researchers initially analyzed the Federal Food and Drug Administration’s Adverse Event Reporting System, examining the frequency of reported liver problems in both men and women. Their findings consistently showed that women reported liver-related adverse events more frequently than men.
Subsequently, the researchers delved into developing computer models of male and female livers, integrating extensive data on gene activity and cellular metabolic processes. These state-of-the-art liver simulations unearthed critical insights into how drugs affect liver tissue differently in men and women, illuminating the reasons behind these disparities.
Connor Moore, a biomedical engineering student in Dr. Papin’s lab, commented, “We were surprised how many differences we found, especially in very diverse biochemical pathways. We hope our results emphasize how important it is for future scientists to consider how both men and women are affected by their research.”
The research has already identified a pivotal series of cellular processes that elucidate the gender-based disparities in liver damage. The scientists are now advocating for further investigation into hepatotoxicity, or liver toxicity, to enhance our understanding of this critical area. Ultimately, they envision their model playing a pivotal role in the development of safer drugs.
Dr. Papin concluded, “We’re hopeful these approaches will help address many other questions where men and women have differences in drug responses or disease processes. Our ability to build predictive computer models of complex systems in biology, like those in this study, is truly opening all kinds of new avenues for tackling some of the most challenging biomedical problems.”
