Overview

• The peer-reviewed study in Science Translational Medicine identifies Kdm6a on the X chromosome as a driver of microglial activation, offering a genetic mechanism for higher female risk in multiple sclerosis and Alzheimer’s disease.
• Genetic deletion of Kdm6a in microglia shifted inflammatory programs toward a resting state and significantly reduced MS-like disease and neuropathology in female mice.
• Pharmacologic knockdown of the same pathway with metformin reproduced benefits in females and produced minimal effects in males.
• Researchers posit that loss of estrogen during menopause may unmask X-linked proinflammatory activity and suggest exploring brain-targeted estrogens.
• The findings are preclinical from a mouse model and will require validation in human biology and rigorous clinical trials before any treatment claims can be made.