A new study undertaken at Tel Aviv University’s Faculty of Medicine and Health Sciences published in the prestigious Translational Psychiatry from Nature journal, found that men and women respond differently to the use of an experimental drug for neurodegenerative diseases like Alzheimer’s, characterized by the pathological accumulation of the tau protein (tauopathy) in brain nerve cells.
The idea for the study arose during a series of studies conducted over the past few years, where significant differences were observed between the results of male and female subjects, both in animal and human models. The first study in which results were separated by gender, focused on the Progressive Supranuclear Palsy (PSP) neurodegenerative disease, where tauopathy is the leading pathology.
The study, conducted in collaboration with students Alexandra Lobyntseva and Jason Blatt, used the experimental drug Davunetide, developed in my laboratory. Davunetide is based on a fragment of the ADNP protein, which is essential for brain creation and function and was previously discovered in research held in my lab.
The effectiveness of this experimental drug, which protects against tauopathy in model systems, has been tested in a series of experiments for various diseases ranging from Alzheimer’s to autism. In the current study, we conducted a data analysis of past clinical trial findings with a separation between men and women.
In the present study, we performed separate data analysis for women and men from findings obtained in a previous clinical trial involving elderly individuals with mild memory impairments indicating a risk for Alzheimer’s disease, which is the most common tauopathy.
The trial assessed short-term visual and verbal memory abilities in 144 elderly participants - 76 women and 68 men. Over three months, the participants were treated daily with a nasal spray of the experimental drug Davunetide and their abilities were tested throughout the period and one month after stopping the drug.
In the separate statistical analysis we recently conducted, high efficacy was found in improving visual memory in men – a 20% improvement on average compared to baseline performance, and an 80% improvement at a six-times higher dose, indicating dose-dependent activity and reinforcing the findings.
In women, the higher dose of the drug led to a 10% improvement on average in verbal attention memory and a reduction in anxiety compared to a slight decline in verbal memory in women who received a placebo.
Additionally, in a data analysis we conducted about a year ago, we found that the condition of women in the placebo group deteriorated faster (over the year of the trial) compared to men in the same group.
However, the experimental drug significantly delayed deterioration in women who received Davunetide, as well as protected the brain and even reduced depressive symptoms, all in line with the drug’s mechanism of action. We are continuing to develop this treatment.
Dr. Ronen Kreizman, CEO of Ramot, the company partnering in the study, said: "The results of this study open a window to a new era in drug development, where gender is a central variable in the design of clinical trials and in the development of the drugs themselves.
“At Ramot, we’re proud to support groundbreaking research like this, which expands the boundaries of medicine and enables the development of innovative treatments for serious diseases."
In conclusion, our findings indicate that in the complex process of drug development, it’s important to consider men and women separately – both in diseases in general and in brain diseases specifically.
We will continue to develop the drug Davunetide and assess its effectiveness for different populations and a range of diseases (including developmental/neurodegenerative brain diseases such as ADNP syndrome, in which we found tauopathy at a young age) while paying attention to gender differences.
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Disclosure:
The advanced research on Davunetide is being held via the Therapeutics ExoNavis company under an exclusive licensing agreement with Ramot, the technology commercialization company of Tel Aviv University, in collaboration with Professor Illana Gozes acting as Vice President for Drug Development at the company.
- Professor Illana Gozes is from the Department of Molecular Genetics and Biochemistry at the School of Medicine and the Sagol School of Neuroscience at Tel Aviv University.