Experimental treatment significantly slows progression of fatal brain disease in women, study finds

Davunetide may significantly slow the progression of a fatal brain disease in women, according to a new analysis of clinical trial data.

The findings indicate that women and men with progressive supranuclear palsy (PSP) may respond differently to the experimental treatment.

Progressive supranuclear palsy, or PSP, is a rare and fatal neurodegenerative disease.

Researchers at Tel Aviv University led the analysis and said the results reinforce the need for sex-specific approaches to neurodegenerative diseases.

Neurodegenerative diseases are conditions in which nerve cells in the brain or nervous system gradually lose function and die.

The team reanalysed data from a 52-week international clinical trial involving more than 300 people with PSP.

The disease is caused by the abnormal accumulation of tau protein in the brain. Tau is a protein found in nerve cells that builds up abnormally in people with PSP.

There is currently no effective drug treatment for the disease.

The work was led by professor Illana Gozes of the Sagol School of Neuroscience and the Gray Faculty of Medical and Health Sciences at Tel Aviv University.

The research team included current and former students Dr Guy Shapira, Jason Blatt and Liri Guz, together with professor Noam Shomron.

The original clinical trial found that Davunetide was safe but ineffective.

However, the researchers separated female and male participants and re-examined the data using updated assessment measures recommended by the FDA.

Women treated with Davunetide experienced a significant slowing of disease progression, while no similar effect was observed in men.

The treatment helped preserve essential movement and functional abilities, including balance, fine motor skills and everyday tasks such as using cutlery, buttoning clothes and washing the face and hands.

Fine motor skills are the small, precise movements needed for tasks involving the fingers and hands.

Treated women also showed significant improvements in language ability, working memory and overall cognitive function.

Cognitive function covers mental abilities such as memory, attention, language and problem-solving.

The analysis also identified profound molecular differences between women and men.

The relationship between levels of pathological tau in cerebrospinal fluid and clinical symptoms was completely reversed between the sexes.

Cerebrospinal fluid is the clear liquid surrounding the brain and spinal cord. A biomarker is a measurable sign that can indicate disease activity.

For example, language abilities declined significantly as tau pathology increased in women, but not in men.

The researchers said this suggests the disease mechanisms may work differently in women and men, potentially explaining their different responses to treatment.

According to professor Gozes, overlooking biological differences between the sexes may hide a genuine treatment effect.

“Our data show that analysing women and men separately is not merely a statistical exercise, but an essential tool for developing more effective treatments for neurodegenerative brain diseases,” she said.

The researchers believe the findings provide a strong scientific basis for future clinical trials and treatment protocols designed from the outset to account for patients’ sex.

These trials could evaluate Davunetide as a targeted treatment for women with PSP.

They said the approach may also pave the way for more precise treatments for tau-related diseases, including Alzheimer’s disease and other neurodegenerative brain disorders.

The study was supported by ExoNavis Therapeutics, which is developing Davunetide for brain diseases under licence from Ramot, Tel Aviv University’s technology transfer company.