The effectiveness of an intranasal drug that failed in a late-stage trial may be influenced by oestrogenSergei Babenko/Alamy
The experimental drug davunetide was showing promise for degenerative brain conditions until, more than 10 years ago, a pivotal late-stage trial fell flat. Allon Therapeutics, the company behind davunetide, subsequently halted its development. But upon closer inspection, scientists found the drug may actually be effective in women. Digging deeper, they have now revealed that fluctuating oestrogen levels may influence how much of the drug reaches the brain, raising the possibility that its effectiveness – and those of other treatments – varies depending on our levels of hormones like oestrogen, which fluctuate throughout the menstrual cycle.
“It’s very common that brain disease is regulated by steroid hormones [such as oestrogen, progesterone and testosterone] and that’s not taken into consideration very often, which is a massive, massive problem,” says Jens Pahnke at the University of Oslo, Norway, who wasn’t involved in the research.
More than 20 years ago, Illana Gozes at Tel Aviv University in Israel derived davunetide from a naturally occurring brain protein called activity-dependent neuroprotective protein (ADNP), which we now know is regulated by sex hormones. Davunetide reinforced microtubules, part of the brain’s transport system, in animal studies. This suggests that microtubules could then more efficiently prevent the toxic build-up of abnormal tau proteins within cells, such as those that form tangles in Alzheimer’s. But in 2014, when an intranasal formulation was put to the test in a late-stage trial for progressive supranuclear palsy – a rare neurological condition driven by abnormal tau accumulation – it didn’t appear to have an effect.
