In our pivotal paper, published in Nature’s Translational Psychiatry, October 2023, we discovered that the tauopathy inhibitor, davunetide shows sex-dependent efficacy in women suffering from progressive supranuclear palsy (PSP). Results revealed accelerated brain degeneration in women compared to men, and significant protection in women, in a one-year study of twice-daily davunetide application (60mg/day). Further significant davunetide protection was observed on geriatric depression. 

Now, extending these findings to elderly individuals suffering from mild cognitive impairments, at risk for Alzheimer’s disease (the major tauopathy), we submitted a double-blind, placebo-controlled clinical trial results to a sex-dependent analysis. 144 individuals, separated into 8 groups (1:2 placebo – and 2 doses, 5mg davunetide/daily or 15 mg davunetide/twice-daily, with matching placebo intranasal volumes) were evaluated. Significant dose-dependent cognitive increases were observed in men compared to women with a test of delayed (12 seconds) visual matching to the sample. In a test of semantic working memory and attention (digit span), women showed a high dose significant davunetide improvement, over the matched placebo. The differential sex-dependent effects on visual and verbal attention/memory found in these studies agree with observations implicating increased spatial memory in men versus enhanced semantic memory in women. The tested women further showed significant anxiety correlations with delayed matching to sample, with anxiety/depression being a risk factor for Alzheimer’s disease and with davunetide protection. In conclusion, sex-specific drug development is encouraged, with davunetide playing a lead initiative role. This new work was just published in Translational Psychiatry (October 2024). 

In summary, in the article "Davunetide sex-dependently boosts memory in prodromal Alzheimer's disease," we explored a previously conducted study on Davunetide's therapeutic capabilities on amnestic mild cognitive impairment. Once sexes were assessed separately, meaningful improvements were seen, varying by sex. Significant dose-dependent spatial cognitive improvements were seen in men compared to women, whereas women showed strong improvements in semantic working memory and attention. Improvements were monitored using a variety of Cambridge Cognition mental acuity, memory, and cognitive assessments. Anxiety was additionally measured, with women showing significant correlations with cognitive performance.

With no approved neuroprotective therapies directly targeting tauopathies like PSP and with Alzheimer's disease being the most prevalent tauopaty, ExoNavis Therapeutics licensed davunetide from Ramot at Tel Aviv University and is striving to further develop davunetide clinically.

Introducing our team, Professor Gozes, the Director of the Elton Laboratory for Molecular Neuroendocrinology at Tel Aviv University and Vice President for Drug Development at ExoNavis therapeutics led the studies, with excellent graduate students and collaborators at Tel Aviv University, supported by the Faculty of Medical and Health Sciences, Sagol School of Neuroscience (Jason Blatt) and Marie Skłodowska-Curie TClock4AD fellowship aimed to discover pharmacological drugs that improve Alzheimer’s disease (Alexandra Lobyntseva).  

Study results are patent protected.