New tool to understand how medications affect men and women differently

UVA Health researchers have pioneered an innovative tool for comprehending the gender-specific effects of medications, paving the way for safer and more efficacious drugs in the future.

Frequently, women experience a disproportionate number of medication-induced liver issues, yet they are often underrepresented in drug trials. To tackle this disparity, UVA scientists have harnessed advanced computer simulations to simulate male and female liver functions, unveiling sex-specific variations in how drugs impact these tissues.

This cutting-edge model has already yielded unprecedented insights into the intricate biological mechanisms within the liver, responsible for detoxification in both genders. Moreover, it stands as a potent asset in drug development, ensuring that new pharmaceuticals do not trigger adverse side effects.

According to Jason Papin, Ph.D., a researcher at UVA, “There exist highly intricate networks of genes and proteins governing cellular responses to drugs. We recognized the necessity of a computer model to tackle these pivotal clinical questions, and we remain optimistic that these models will continually provide insights to enhance healthcare.”

Harmful effects from drugs

Papin, a member of UVA’s Department of Biomedical Engineering, collaborated with Connor Moore, a Ph.D. student, and Dr. Christopher Holstege, MD, an emergency medicine physician and director of UVA Health’s Blue Ridge Poison Center, to develop this groundbreaking model. Dr. Holstege stressed the crucial importance of ensuring that both men and women receive the correct dosage of prescribed medications, given the complexity of drug therapy and the potential for toxicity with slight dosage variations for individual patients.

Prior to creating their model, the research team delved into the federal Food and Drug Administration’s Adverse Event Reporting System to analyze the frequency of reported liver-related issues in both sexes. Their findings revealed a consistent trend: women reported liver-related adverse events more frequently than men.

To understand this phenomenon, the scientists engineered computer models of male and female livers, incorporating extensive data on gene activity and cellular metabolic processes. These state-of-the-art liver simulations provided valuable insights into the differential impact of drugs on liver tissue in men and women, shedding light on the underlying reasons.

Connor Moore, a biomedical engineering student working in Papin’s lab, remarked, “We were taken aback by the multitude of disparities we discovered, especially in diverse biochemical pathways. We hope our findings underscore the importance of future researchers considering the effects on both men and women in their studies.”

This research has already pinpointed a critical set of cellular processes that elucidate gender-based differences in liver damage, prompting a call for further investigation into “hepatotoxicity”—liver toxicity. Ultimately, the researchers anticipate that their model will prove invaluable in the development of safer medications.

Jason Papin expressed optimism about the broader implications of their approach, saying, “We believe that these methods can address many other questions involving divergent drug responses or disease processes in men and women. Our capacity to construct predictive computer models for intricate biological systems, as demonstrated in this study, is opening up new avenues for tackling some of the most challenging biomedical issues.”

The researchers have published their findings in PLOS Computational Biology.

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