Sarah Berga, MD, Discusses Why Industry Must Consider Sex Differences in Drug Development
Since the 1980s, researchers at Wake Forest School of Medicine have been active in understanding hormones and health and other aspects of women’s health such as the effects of postmenopausal hormone therapy and soy diets on health, sex differences in cognitive function in the elderly, and the ways that cardiovascular disease manifests differently in women and men. Now, led by Sarah Berga, MD, professor and chair of obstetrics and gynecology and vice president of women’s health at Wake Forest School of Medicine, they are asking questions that may soon revolutionize how industry develops therapeutics.
Sex Differences in Our Cells
“Every cell in the body has a sex and the sex of the cells can cause function and behavior to vary,” says Berga. “XX cells and XY cells have different cellular machinery and what that means is diseases or conditions present differently in men and women or require different interventions or diagnostics.”
For example, XY neurons and XX neurons, when subjected to an anoxic insult, die by different cellular pathways, an occurrence that scientists do not fully understand, though a similar phenomenon happens to male and female placentas. Sex differences also affect the prevalence and presentation of autoimmune diseases, cardiovascular diseases and neurodegenerative disorders. Even men’s bones differ significantly from those of women.
Wake Forest’s researchers have also found that glucocorticoids differently impact male and female fetuses and that the impact persists into adulthood. Clinicians give glucocorticoids to women in preterm labor to help develop the lungs of babies born prematurely. The research shows, however, that boys exposed to glucocorticoids before birth have a higher incidence of cardiovascular disease as they age, while girls are relatively unaffected. Berga asks, given this sex difference, should doctors still administer glucocorticoids to boys preterm, or should research be done to find a better alternative?
“The idea that there are sex differences is not really new,” she says. “However, the idea that men and women are, at the molecular level, different and could react in opposite ways still surprises people.”
Berga’s goal is to turn this surprise into the motivation needed for more in-depth research into the role of sex in therapeutic efficacy.
Charting the Path Forward
“People have been under-inspired to look into sex differences until recently because testing is complex and it makes more work to delineate and understand sex differences,” says Berga. However, she notes, the two most important factors in individualized diagnosis and treatment are sex and age.
“Give me the drug that works for me,” she says, “not the drug that works for my opposite sex.”
To help develop more individualized treatments, drug development teams should include sex difference specialists in study design and analysis. These specialists could ask questions about the impacts of sex differences that are commonly overlooked and help guide study design to account for these differences.
“Industry can change preclinical and clinical trial standards by giving researchers the power to look for sex differences,” she says.
Berga is hopeful that these industry-academia partnerships can support sex-specific diagnostic and treatment strategies tailored to meet the needs of individual patients.
“Our focus should be on how to use the fact that men and women respond differently when administered medications to positive advantage in research to be better able to anticipate whether and how side effects, dose regimens and outcomes differ between men and women,” says Berga. “The goal is to develop drugs that work and are safe and we can do this better if we understand sex differences at the pharmacologic, physiologic and cellular levels. This is the way to drive more personalized care.”
Partnering with Wake Forest
The vision of and commitment to women’s health at Wake Forest makes it the ideal partner to help industry investigate the relationship between sex differences and therapeutic efficacy.
“Wake Forest has a long history of wanting to answer these types of questions,” says Berga. “We have been looking at sex differences for decades and we are well prepared to help industry navigate this area of investigation.”
Berga and her scientist and clinician colleagues at Wake Forest offer a unique perspective for industry partners seeking to better understand the implications of sex differences on research, wisdom that may save time, effort and money during key phases of drug development.
Schedule a meeting with Wake Forest Innovations to discuss your next preclinical study or clinical trial.