Abstract: TH-PO116
Evaluating Sex-Biased Adverse Event-Associated Drugs to Improve Kidney Disease Drug Prioritization
Session Information
- Pharmacology
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Lasseigne, Brittany N., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Howton, Timothy C., The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Wilk, Elizabeth, The University of Alabama at Birmingham, Birmingham, Alabama, United States
Group or Team Name
- Lasseigne Lab.
Background
Sex differences impact disease pathology, including kidney diseases (e.g., polycystic kidney disease, PKD; acute kidney injury, AKI). Also, women are more likely to have drug-related adverse events (unintended medication effects), and men are more likely to experience events resulting in hospitalization or death. These sex-biased adverse events (SBAEs) are due to many factors, but it is critical to evaluate the impact of sex when prioritizing drug targets and repurposing candidates.
Methods
Previously, we evaluated sex-specific gene expression (GE) of known drug targets and metabolism enzymes for SBAE-associated drugs. We also assessed sex-biased GE and gene-regulatory network properties for 45 tissues to determine if known SBAE-associated drug targets and metabolism enzymes had sex-specific gene properties. We applied these findings to drugs approved for or in clinical trials to treat PKD, AKI, and other kidney diseases.
Results
We found ~85% of SBAE-associated targets had sex-biased GE or were core genes of sex- and tissue-specific network communities and demonstrated these data can prioritize drugs for preclinical/clinical kidney disease trials.
Conclusion
Our approach may be useful for studies seeking to explain or predict SBAEs, critical for realizing precision medicine for kidney-associated diseases.
1. Sex-biased drug-adverse event pairs.
2. Sex-biased GE of PKD drug targets.
Funding
- Other NIH Support