Opposite molecular sex correlations in tauopathy paralleled by motor and cognitive efficacy of davunetide in women.

Shapira G, Blatt J, Guz LS, Shomron N, Gozes I

Molecular psychiatry3 Jul 2026Cited by 1 (Europe PMC)

PMID42399413PMCIDPMC13668703DOI10.1038/s41380-026-03709-xPepBankPUB-42399413

Summary

Progressive supranuclear palsy (PSP) is a fatal tauopathy presenting an unmet medical need. Davunetide, targeting tauopathy, has been previously tested in PSP, which, when separated by sex, implied efficacy in women. Here, efficacy was evaluated using longitudinal data (52 weeks) and applying for the first time, the US Food and Drug Administration (FDA) -recommended 10-item PSP Rating Scale (PSPRS-10) compared to the 28-item PSPRS (primary endpoint). Time-, sex-, and treatment-related effects were analyzed using linear mixed-effects models including the FDA-recommended Mixed Models for Repeated Measures (MMRM). Cognitive evaluations used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Clinical analyses at the individual level accentuated the impact of the 10 PSPRS chosen items and revealed a significant treatment effect favoring women when accounting for time, sex, and treatment interactions (P = 0.0005). Motor measurements were highlighted. RBANS analyses demonstrated women's significant improvements in total raw score, letter-number sequencing, and language scores. Correlating cerebrospinal fluid (CSF) phosphorylated Tau/Tau with functional outcomes revealed significance with p-Tau/Tau ratio and grasping/imitative/utilizing behavior (assessing involuntary actions in PSPRS-28). This correlation was opposite in direction between females (r = 0.77; P = 0.006) and males (r = -0.62; P = 0.075), with sex difference showing a P = 0.0002 value. Similar results were obtained for language. Predicting the final PSPRS score (week 52), addressing all clinical measures, a clear woman-treatment-specific pattern in outcome importance was discovered, highlighting significance for the primary endpoint Schwab and England Activity of Daily Living (SEADL) scale, and stressing the necessity for sex-specific medicine with davunetide as a lead compound.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

4 results from studies that gave the peptide. 4 results from people.

01HumanObservational studyEfficacy outcome
In patients with progressive supranuclear palsy, clinical analyses of the 10 chosen PSPRS items found a significant davunetide treatment effect favoring women when accounting for time, sex, and treatment interactions.
In plain wordsIn people with progressive supranuclear palsy, a clinical analysis found a significant davunetide treatment effect favoring women.
Peptide
Davunetide
Outcome
Direction not reportedPSPRS treatment effect in women
Study
n: not reported in source
Outcome group
Exercise and physical function · Nervous system and cognition
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Measurements
Treatment interaction P value
0.0005
time, sex, and treatment interactions
Source sentences
Summary
Clinical analyses at the individual level accentuated the impact of the 10 PSPRS chosen items and revealed a significant treatment effect favoring women when accounting for time, sex, and treatment interactions (P = 0.0005).
3 context sentences(design, population, supporting numbers)
Summary · context
Here, efficacy was evaluated using longitudinal data (52 weeks) and applying for the first time, the US Food and Drug Administration (FDA) -recommended 10-item PSP Rating Scale (PSPRS-10) compared to the 28-item PSPRS (primary endpoint).
Summary · context
Time-, sex-, and treatment-related effects were analyzed using linear mixed-effects models including the FDA-recommended Mixed Models for Repeated Measures (MMRM).
Summary · context
Cognitive evaluations used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Show in the study text Report a problemFND-4239941301
02HumanObservational studyEfficacy outcome
In women with progressive supranuclear palsy, RBANS analyses showed significant improvement in total raw score.
In plain wordsIn women with progressive supranuclear palsy, RBANS total scores improved significantly.
Peptide
Davunetide
Outcome
IncreaseRBANS total raw score
Study
n: not reported in source
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
RBANS analyses demonstrated women's significant improvements in total raw score, letter-number sequencing, and language scores.
3 context sentences(design, population, supporting numbers)
Summary · context
Here, efficacy was evaluated using longitudinal data (52 weeks) and applying for the first time, the US Food and Drug Administration (FDA) -recommended 10-item PSP Rating Scale (PSPRS-10) compared to the 28-item PSPRS (primary endpoint).
Summary · context
Time-, sex-, and treatment-related effects were analyzed using linear mixed-effects models including the FDA-recommended Mixed Models for Repeated Measures (MMRM).
Summary · context
Cognitive evaluations used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Show in the study text Report a problemFND-4239941302
03HumanObservational studyEfficacy outcome
In women with progressive supranuclear palsy, RBANS analyses showed significant improvement in letter-number sequencing.
In plain wordsIn women with progressive supranuclear palsy, letter-number sequencing scores improved significantly.
Peptide
Davunetide
Outcome
IncreaseLetter-number sequencing
Study
n: not reported in source
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
RBANS analyses demonstrated women's significant improvements in total raw score, letter-number sequencing, and language scores.
3 context sentences(design, population, supporting numbers)
Summary · context
Here, efficacy was evaluated using longitudinal data (52 weeks) and applying for the first time, the US Food and Drug Administration (FDA) -recommended 10-item PSP Rating Scale (PSPRS-10) compared to the 28-item PSPRS (primary endpoint).
Summary · context
Time-, sex-, and treatment-related effects were analyzed using linear mixed-effects models including the FDA-recommended Mixed Models for Repeated Measures (MMRM).
Summary · context
Cognitive evaluations used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Show in the study text Report a problemFND-4239941303
04HumanObservational studyEfficacy outcome
In women with progressive supranuclear palsy, RBANS analyses showed significant improvement in language scores.
In plain wordsIn women with progressive supranuclear palsy, language scores improved significantly.
Peptide
Davunetide
Outcome
IncreaseLanguage score
Study
n: not reported in source
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
RBANS analyses demonstrated women's significant improvements in total raw score, letter-number sequencing, and language scores.
3 context sentences(design, population, supporting numbers)
Summary · context
Here, efficacy was evaluated using longitudinal data (52 weeks) and applying for the first time, the US Food and Drug Administration (FDA) -recommended 10-item PSP Rating Scale (PSPRS-10) compared to the 28-item PSPRS (primary endpoint).
Summary · context
Time-, sex-, and treatment-related effects were analyzed using linear mixed-effects models including the FDA-recommended Mixed Models for Repeated Measures (MMRM).
Summary · context
Cognitive evaluations used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Show in the study text Report a problemFND-4239941304

Studies that did not test the peptide alone1

In this study, Davunetide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Davunetide.

05HumanNot a test of Davunetide aloneObservational studyOther
In women with progressive supranuclear palsy, final PSPRS prediction identified a treatment-specific outcome-importance pattern highlighting SEADL significance.
In plain wordsIn women with progressive supranuclear palsy, outcome prediction showed a treatment-specific pattern highlighting the daily living scale.
Peptide
Davunetide
Outcome
Not applicableOutcome importance for final PSPRS prediction
Study
n: not reported in source
Outcome group
Exercise and physical function · Nervous system and cognition
Source sentences
Summary
Predicting the final PSPRS score (week 52), addressing all clinical measures, a clear woman-treatment-specific pattern in outcome importance was discovered, highlighting significance for the primary endpoint Schwab and England Activity of Daily Living (SEADL) scale,
3 context sentences(design, population, supporting numbers)
Summary · context
Here, efficacy was evaluated using longitudinal data (52 weeks) and applying for the first time, the US Food and Drug Administration (FDA) -recommended 10-item PSP Rating Scale (PSPRS-10) compared to the 28-item PSPRS (primary endpoint).
Summary · context
Time-, sex-, and treatment-related effects were analyzed using linear mixed-effects models including the FDA-recommended Mixed Models for Repeated Measures (MMRM).
Summary · context
Cognitive evaluations used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
In this study, Davunetide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Davunetide.
Show in the study text Report a problemFND-4239941305

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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