A study in Israel has found that an experimental drug for brain disorders reaches the brain differently depending on the stage of the reproductive cycle of female mice.
Davunetide (NAP) is an experimental drug designed to protect nerve cells in brain diseases associated with ageing. Previous clinical studies suggested that a nasal spray with this drug for progressive supranuclear palsy, a severe degenerative brain disease, works better in women than in men, but the reasons for these differences were unclear.
Researchers at Tel Aviv University investigated whether biological sex and hormone levels could affect how the drug travels through the head and body. By attaching a fluorescent molecule to the drug, they were able to track its distribution in real time with a microscope after administering it through the nose of male and female mice.
The researchers found that, in female mice, more drug reached the head during phases of their reproductive cycle when oestrogen levels were highest. When oestrogen levels were lower, the differences between female and male mice largely disappeared.
The team also analysed data from a previous study to test the safety of the drug in healthy adults. They found that women tended to reach higher concentrations of the drug, while men retained it for longer, suggesting that biological sex in humans may influence how the body processes the drug.
“These sex-specific differences likely reflect a combination of hormonal regulation, tissue distribution, nasal physiology, and blood-brain barrier function,” the authors concluded in the study published in Genomic Psychiatry.
The findings suggest that sex and hormone levels may influence how medicines reach the brain and could affect their efficiency. This knowledge could help researchers develop more effective treatments by considering sex differences when designing and testing new medicines.