Rhonda Voskuhl, MD: Investigating the XY factor in disease

Rhonda R. Voskuhl, MD

"Scientists are beginning to understand how sex chromosomes and hormones affect people's risk for certain diseases — and whether the biology behind those differences can be harnessed to improve treatments.

Why it matters: Doctors and scientists have long recognized certain diseases affect men and women differently but that is rarely reflected in the dosage and design of drugs.

Driving the news: A newly approved drug for Alzheimer's disease may be less effective for women — who are more likely to develop the disease over their lifetime — than men, my Axios colleagues reported this week.

What's happening: Study after study has described the differences in the impact of disease between males and females.

  • In the U.S., 80% of people who have an autoimmune disease are female. Rheumatoid arthritis, Hashimoto's disease, and multiple sclerosis all affect women more than men.
  • Men are more likely to develop severe COVID but emerging evidence suggests long COVID is more common among women.
  • Nearly two-thirds of people age 65 and older in the U.S. with Alzheimer's disease are women.

Details: Researchers are beginning to understand the molecular underpinnings of these differences.-The X chromosome encodes several genes known to be involved in stimulating the immune system.

  • One study found a gene on the X chromosome is expressed more in the immune cells of females than in males. When researchers deleted the gene in mice that had been bred to have an autoimmune disease similar to MS, they had fewer symptoms. The activity of genes related to healthy immune activity also increased and the activity of those involved in inflammation in the brain decreased.

The effects from the expression of genes on the X and Y chromosomes are overlaid with the effects of hormones in males and females, which can change over time, says UCLA professor of neurology Rhonda Voskuhl, a co-author of the study.

  • Researchers have also found estrogen is neuroprotective and anti-inflammatory.
  • That aligns with the symptoms of MS worsening for women during menopause when estrogen levels drop, healthy women experiencing cognitive difficulties during menopause and women's risk for developing Alzheimer's disease increasing after menopause."

Read more at Axios.