2023-10-05 16:00:00
UVA Health researchers have developed a powerful new tool to understand how medications affect men and women differently, which would help generate safer and more effective medicines.
According to UVA Health, women suffer a disproportionate number of liver problems due to medications. At the same time, they are often underrepresented in drug testing. To address this, UVA scientists have developed sophisticated computer simulations of male and female livers, aiming to reveal specific differences and how tissues are affected by medicines.
The new model has already provided unprecedented information regarding the biological processes taking place in the liver, the organ responsible for detoxifying the body, in both men and women. But the model also represents a powerful new tool for drug development, helping to ensure that new drugs do not cause harmful side effects.
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“There are incredibly complex networks of genes and proteins that control how cells respond to drugs,” said UVA researcher Jason Papin, Ph.D., one of the model’s creators. “We knew that a computational model would be needed to try to answer these important clinical questions, and we are hopeful that these models will continue to provide insights that can improve healthcare.”
The researchers published their findings in the scientific journal PLOS Computational Biology.
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Papin, of UVA’s Department of Biomedical Engineering, developed the model in collaboration with Connor Moore, a doctoral student, and Christopher Holstege, MD, a UVA emergency physician and director of the Blue Ridge Poison Center at UVA Health. “It is extremely important that both men and women receive the proper dosage of recommended medications,” Holstege said. “Drug therapy is complex and people can become poisoned with subtle changes in dosage.”
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Before developing their model, the researchers first looked at the federal Food and Drug Administration’s Adverse Event Reporting System to assess the frequency of liver problems in men and women. The scientists found that women consistently reported liver-related adverse events, even more than men.
The researchers then tried to explain why this might be the case. To do this, they developed computer models of male and female livers that integrated large amounts of data on genetic activity and metabolic processes within cells. These liver simulations provided important information regarding how drugs affect the tissue differently in men and women and allowed researchers to understand why.
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“We were surprised by how many differences we found, especially in very diverse biochemical pathways,” said Moore, a biomedical engineering student in Papin’s lab. “We hope our results emphasize how important it is for future scientists to consider how their research affects both men and women.”
The work has already identified a key series of cellular processes that explain differences in liver damage, and scientists are calling for more research to better understand “hepatotoxicity” – liver toxicity. Ultimately they hope their model will prove widely useful in the development of safer drugs.
“We are hopeful that these approaches will help address many other issues where men and women have differences in responses to medications or disease processes,” Papin said. “Our ability to build predictive computer models of complex systems in biology, like those in this study, is really opening up all kinds of new avenues for addressing some of the most challenging biomedical problems.” (YO)
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