Researchers in the US have developed a powerful new tool to understand how medications affect men and women differently, and that will help lead to safer, more effective drugs in the future.
Women are known to suffer a disproportionate number of liver problems from certain medications.
They are also typically underrepresented in drug testing.
To address this, researchers at the University of Virginia (UVA) have developed sophisticated computer simulations of male and female livers and used them to reveal sex-specific differences in how the tissues are affected by drugs.
The new model has already provided unprecedented insights into the biological processes that occur 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 ensure that new medications do not cause harmful side effects.
UVA researcher Jason Papin, PhD, one of the model’s creators, said: “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.”
Papin, of UVA’s Department of Biomedical Engineering, developed the model alongside Connor Moore, a PhD student, and Christopher Holstege, MD, a UVA emergency medicine physician and director of UVA Health’s Blue Ridge Poison Center.
Holstege said:
“It is exceedingly important that both men and women receive the appropriate dose of recommended medications.
“Drug therapy is complex and toxicity can occur with subtle changes in dose for specific individuals.”
Before developing their model, the scientists first looked at the federal Food and Drug Administration’s Adverse Event Reporting System to evaluate the frequency of reported liver problems in men and women.
The researchers found that women consistently reported liver-related adverse events more often than did men.
The team then sought to explain why this might be the case.
To do that, the scientists developed computer models of the male and female livers that integrated vast amounts of data on gene activity and metabolic processes within cells.
These cutting-edge liver simulations provided invaluable insights into how drugs affect the tissue differently in men and women and allowed the researchers to understand why.
Moore, a biomedical engineering student in Papin’s lab, said: “We were surprised how many differences we found, especially in very diverse biochemical pathways.
“We hope our results emphasise how important it is for future scientists to consider how both men and women are affected by their research.”
The work has already identified a key series of cellular processes that explain sex differences in liver damage, and the researchers are calling for more investigation of it to better understand “hepatotoxicity” – liver toxicity.
Ultimately, the team hope their model will prove widely useful in developing safer drugs.
Papin said:
“We’re hopeful these approaches will be 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.”
