Unexpected gender differences in progressive supranuclear palsy reveal efficacy for davunetide in women.

Gozes I, Shapira G, Lobyntseva A, Shomron N

Translational psychiatry16 Oct 2023Cited by 19 (Europe PMC)

PMID37845254PMCIDPMC10579238DOI10.1038/s41398-023-02618-9PepBankPUB-37845254

Summary

Progressive supranuclear palsy (PSP) is a pure tauopathy, implicating davunetide, enhancing Tau-microtubule interaction, as an ideal drug candidate. However, pooling patient data irrespective of sex concluded no efficacy. Here, analyzing sex-dependency in a 52 week-long- PSP clinical trial (involving over 200 patients) demonstrated clear baseline differences in brain ventricular volumes, a secondary endpoint. Dramatic baseline ventricular volume-dependent/volume increase correlations were observed in 52-week-placebo-treated females (r = 0.74, P = 2.36^-9), whereas davunetide-treated females (like males) revealed no such effects. Assessment of primary endpoints, by the PSP Rating Scale (PSPRS) and markedly more so by the Schwab and England Activities of Daily Living (SEADL) scale, showed significantly faster deterioration in females, starting at trial week 13 (P = 0.01, and correlating with most other endpoints by week 52). Twice daily davunetide treatments slowed female disease progression and revealed significant protection according to the SEADL scale as early as at 39 weeks (P = 0.008), as well as protection of the bulbar and limb motor domains considered by the PSPRS, including speaking and swallowing difficulties caused by brain damage, and deterioration of fine motor skills, respectably (P = 0.01), at 52 weeks. Furthermore, at 52 weeks of trial, the exploratory Geriatric Depression Scale (GDS) significantly correlated with the SEADL scale deterioration in the female placebo group and demonstrated davunetide-mediated protection of females. Female-specific davunetide-mediated protection of ventricular volume corresponded to clinical efficacy. Together with the significantly slower disease progression seen in men, the results reveal sex-based drug efficacy differences, demonstrating the neuroprotective and disease-modifying impact of davunetide treatment for female PSP patients.

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

Results from this study6

5 results from studies that gave the peptide. 5 results from people.

01HumanNon-randomized trialEfficacy outcome
In women with PSP, twice-daily davunetide significantly protected SEADL performance as early as 39 weeks.
In plain wordsIn women with PSP, davunetide slowed loss of daily function by 39 weeks.
Peptide
Davunetide
Outcome
DecreaseSEADL disease progression
Study
n: not reported in source
Analysis
Primary
Outcome group
Exercise and physical function · Nervous system and cognition
Studied dose
Dose not stated · 39 weeksAs given in this study (human).
Measurements
P value
0.008 NA
women, davunetide, SEADL at week 39
Source sentences
Summary
Twice daily davunetide treatments slowed female disease progression and revealed significant protection according to the SEADL scale as early as at 39 weeks (P = 0.008)
1 context sentence(design, population, supporting numbers)
Summary · context
Here, analyzing sex-dependency in a 52 week-long- PSP clinical trial (involving over 200 patients) demonstrated clear baseline differences in brain ventricular volumes, a secondary endpoint.
Show in the study text Report a problemFND-3784525402
02HumanNon-randomized trialEfficacy outcome
In women with PSP, davunetide-mediated protection of ventricular volume corresponded to clinical efficacy.
In plain wordsIn women with PSP, protection of ventricular volume with davunetide corresponded to clinical benefit.
Peptide
Davunetide
Outcome
Direction not reportedVentricular volume protection
Study
n: not reported in source
Analysis
Secondary
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Female-specific davunetide-mediated protection of ventricular volume corresponded to clinical efficacy.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, analyzing sex-dependency in a 52 week-long- PSP clinical trial (involving over 200 patients) demonstrated clear baseline differences in brain ventricular volumes, a secondary endpoint.
Show in the study text Report a problemFND-3784525406
03HumanNon-randomized trialEfficacy outcome
In women with PSP, the Geriatric Depression Scale demonstrated davunetide-mediated protection at 52 weeks.
In plain wordsIn women with PSP, the depression scale showed protection with davunetide at 52 weeks.
Peptide
Davunetide
Outcome
Direction not reportedGeriatric Depression Scale protection
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
Dose not stated · 52 weeksAs given in this study (human).
Source sentences
Summary
Furthermore, at 52 weeks of trial, the exploratory Geriatric Depression Scale (GDS) significantly correlated with the SEADL scale deterioration in the female placebo group and demonstrated davunetide-mediated protection of females.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, analyzing sex-dependency in a 52 week-long- PSP clinical trial (involving over 200 patients) demonstrated clear baseline differences in brain ventricular volumes, a secondary endpoint.
Show in the study text Report a problemFND-3784525405
04HumanNon-randomized trialEfficacy outcome
In women with PSP, davunetide protected the PSPRS bulbar motor domain at 52 weeks.
In plain wordsIn women with PSP, davunetide protected bulbar motor function at 52 weeks.
Peptide
Davunetide
Outcome
DecreasePSPRS bulbar motor domain
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
P value
0.01 NA
women, PSPRS bulbar domain, week 52
Source sentences
Summary
as well as protection of the bulbar and limb motor domains considered by the PSPRS, including speaking and swallowing difficulties caused by brain damage, and deterioration of fine motor skills, respectably (P = 0.01), at 52 weeks.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, analyzing sex-dependency in a 52 week-long- PSP clinical trial (involving over 200 patients) demonstrated clear baseline differences in brain ventricular volumes, a secondary endpoint.
Show in the study text Report a problemFND-3784525403
05HumanNon-randomized trialEfficacy outcome
In women with PSP, davunetide protected the PSPRS limb motor domain at 52 weeks.
In plain wordsIn women with PSP, davunetide protected limb motor function at 52 weeks.
Peptide
Davunetide
Outcome
DecreasePSPRS limb motor domain
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
P value
0.01 NA
women, PSPRS limb motor domain, week 52
Source sentences
Summary
as well as protection of the bulbar and limb motor domains considered by the PSPRS, including speaking and swallowing difficulties caused by brain damage, and deterioration of fine motor skills, respectably (P = 0.01), at 52 weeks.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, analyzing sex-dependency in a 52 week-long- PSP clinical trial (involving over 200 patients) demonstrated clear baseline differences in brain ventricular volumes, a secondary endpoint.
Show in the study text Report a problemFND-3784525404

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.

06HumanNot a test of Davunetide aloneObservational studyEfficacy outcome
In women with PSP in a 52-week trial, baseline ventricular volume correlated with ventricular volume increase in placebo-treated women (r = 0.74) but not in davunetide-treated women.
In plain wordsIn women with PSP, starting brain ventricle size was linked to later ventricle growth with placebo but not with davunetide.
Peptide
Davunetide
Outcome
No significant changeBaseline ventricular volume and volume increase correlation
Study
n: not reported in source
Comparator
Placebo-treated females
Analysis
Secondary
Outcome group
Neuroprotection · Nervous system and cognition
Measurements
Correlation of baseline ventricular volume with volume increase
0.74 r
placebo-treated females, 52 weeks
Source sentences
Summary
Dramatic baseline ventricular volume-dependent/volume increase correlations were observed in 52-week-placebo-treated females (r = 0.74, P = 2.36^-9), whereas davunetide-treated females (like males) revealed no such effects.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, analyzing sex-dependency in a 52 week-long- PSP clinical trial (involving over 200 patients) demonstrated clear baseline differences in brain ventricular volumes, a secondary endpoint.
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-3784525401

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

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