Experimental Drug Davunetide Slows Progression of Rare Brain Disease PSP in Women, Reanalysis Reveals
核心洞察
Reanalysis of a 52-week international clinical trial of over 300 PSP patients found that Davunetide significantly slowed disease progression in women but not men.
Treated women preserved key daily functions including balance, fine motor skills, and cognitive abilities such as memory and language.
Researchers discovered profound molecular differences between sexes, with tau pathology–symptom relationships reversed in women versus men.
A reanalysis of clinical trial data has revealed that the experimental drug Davunetide significantly slows disease progression in women with progressive supranuclear palsy (搜索) (PSP), a rare and fatal neurodegenerative disorder, challenging the original conclusion that the drug was ineffective. The findings, led by researchers at Tel Aviv University and published in Molecular Psychiatry from the Nature portfolio, underscore the critical importance of accounting for biological sex differences when evaluating treatments for brain diseases.
The original 52-week international clinical trial, which enrolled more than 300 patients with PSP, had concluded that Davunetide—a tauopathy-targeting drug—was safe but showed no overall efficacy. However, the Tel Aviv University team, led by Prof. Illana Gozes of the Sagol School of Neuroscience and the Gray Faculty of Medical and Health Sciences, conducted an advanced reanalysis using updated FDA-recommended outcome measures and stratified participants by sex. The results painted a markedly different picture.
Sex-Specific Efficacy Emerges
When the researchers examined women and men separately, they found that women who received Davunetide experienced a significant slowdown in disease progression, while no similar benefit was observed in men. The treatment helped women preserve essential motor and functional abilities, including balance, fine motor skills, and everyday activities such as using cutlery, buttoning clothes, and washing the face and hands. In addition, treated women showed significant improvements in cognitive measures, including language abilities, working memory, and overall cognitive function.
"Our data show that analyzing women and men separately is not merely a statistical exercise, but an essential tool for developing more effective treatments for neurodegenerative brain diseases," said Prof. Gozes.
Molecular Differences Between Sexes
Beyond the clinical outcomes, the study uncovered profound molecular differences between female and male patients. The researchers found that the relationship between pathological tau levels in cerebrospinal fluid—a key biomarker of the disease—and clinical symptoms was completely reversed between the two sexes. For instance, language abilities significantly decreased with increased tau pathology in women, but not in men. This finding suggests that the underlying disease mechanisms may operate differently in women and men, potentially explaining their divergent responses to treatment.
Implications for Future Research
PSP is caused by the abnormal accumulation of tau protein (搜索) in the brain and currently has no effective drug treatment. The researchers believe their findings provide a strong scientific basis for future clinical trials designed from the outset to account for patients' sex, evaluating Davunetide as a targeted treatment for women with PSP. They further suggest that this approach may pave the way for more precise medicine in tau-related diseases, including the far more common Alzheimer's disease and other neurodegenerative disorders.
The study was supported by ExoNavis Therapeutics (搜索), which is developing Davunetide for brain diseases under a license from Ramot (搜索), Tel Aviv University's technology transfer company. Prof. Gozes serves as the company's Vice President for Drug Development, and Dr. Guy Shapira serves as a consulting statistician. The results were independently validated by several additional statisticians.