Daijiworld Media Network - New Delhi

New Delhi, Oct 18: A team of US researchers has identified a gene on the X chromosome that may explain why women are more prone to brain-related inflammatory conditions such as Alzheimer’s disease and multiple sclerosis (MS). The findings, published in Science Translational Medicine, point to the gene Kdm6a as a key driver of inflammation in the female brain — and a potential target for treatment.

The study, led by scientists at the University of California–Los Angeles (UCLA), revealed that because women possess two X chromosomes compared to one in men, they receive a "double dose" of inflammation-triggering genetic activity. This may underlie why women are two to three times more likely to develop MS or Alzheimer’s, and why many experience cognitive symptoms such as "brain fog" during menopause.

Using a mouse model for multiple sclerosis, researchers showed that Kdm6a activates inflammation in microglia — the brain’s resident immune cells. When the gene or its protein product was deactivated, disease symptoms and neural damage in female mice were significantly reduced.

Lead author Dr. Rhonda Voskuhl, director of UCLA Health’s Multiple Sclerosis Program, explained, “When we knocked out Kdm6a in brain immune cells, inflammatory molecules shifted from an activated to a resting state. The results were striking in female mice, while barely detectable in males.”

The study also tested the diabetes drug metformin as a means of "knocking down" the Kdm6a protein pharmacologically. Again, the intervention showed strong therapeutic effects in females but minimal impact in males — highlighting a possible sex-based difference in treatment response.

“This is consistent with there being more to block in females due to having two copies of the X-linked gene,” said Voskuhl. “It’s also why females are more likely to get MS and Alzheimer’s than males. This has implications for the clinic. Women may respond differently to metformin treatment than men.”

The findings pave the way for more sex-specific approaches in treating neuroinflammatory and neurodegenerative diseases, and suggest that targeting X-linked genes like Kdm6a could offer new hope for millions of women affected by these conditions.