The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial
Open accessAbstract
Background In preclinical studies, davunetide promoted microtubule stability and reduced tau phosphorylation. Because progressive supranuclear palsy (PSP) is linked to tau pathology, davunetide could be a treatment for PSP. We assessed the safety and efficacy of davunetide in patients with PSP.Methods In a double-blind, parallel group, phase 2/3 trial, participants were randomly assigned with permuted blocks in a 1:1 ratio to davunetide (30 mg twice daily, intranasally) or placebo for 52 weeks at 48 centres in Australia, Canada, France, Germany, the UK, and the USA. Participants met the modified Neuroprotection and Natural History in Parkinson Plus Syndrome study criteria for PSP. Primary endpoints were the change from baseline in PSP Rating Scale (PSPRS) and Schwab and England Activities of Daily Living (SEADL) scale at up to 52 weeks. All participants and study personnel were masked to treatment assignment. Analysis was by intention to treat. The trial is registered with Clinicaltrials.gov, number NCT01110720.Findings 313 participants were randomly assigned to davunetide (n=157) or to placebo (n=156), and 241 (77%) completed the study (118 and 156 in the davunetide and placebo groups, respectively). There were no differences in the davunetide and placebo groups in the baseline PSPRS and SEADL. The davunetide and placebo groups did not differ in the change from baseline in PSPRS (median 11·8 [95% CI 10·5 to 13·0] vs 11·8 [10·5 to 13·0], respectively, p=0·41) or SEADL (-0·20 [-0·20 to -0·17] vs -0·20 [-0·22 to -0·17], respectively, p=0·92). 54 serious adverse events were reported in each of the treatment groups, including 11 deaths in the davunetide group and ten in the placebo group. The frequency of nasal adverse events was greater in the davunetide group than in the placebo group (epistaxis 18 [12%] of 156 vs 13 [8%] of 156, rhinorrhoea 15 [10%] vs eight [5%], and nasal discomfort 15 [10%] vs one [<1%]).Interpretation Davunetide is not an effective treatment for PSP. Clinical trials of disease-modifying treatment are feasible in patients with PSP and should be pursued with other promising tau-directed treatments.Funding Allon Therapeutics.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the latest phase II/III study162, patients with PSP were treated with NAP for 52 weeks, but no differences were found between placebo-treated and NAP-treated patients163.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [163]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Development and validation of a geriatric depression screening scale: a preliminary report
Yesavage, J. A., Brink, T. L., Rose, T. L., Lum, O., Huang, V., Adey, M., & Leirer, V. O. (1982) · Journal of Psychiatric Research · doi:10.1016/0022-3956(82)90033-4 · Cited by 15,025
Randolph, C., Tierney, M. C., Mohr, E., & Chase, T. N. (1998) · Journal of Clinical and Experimental Neuropsychology · doi:10.1076/jcen.20.3.310.823 · Cited by 2,519
Self-citationProgressive Supranuclear Palsy
Steele, J. C. (1964) · Archives of Neurology · doi:10.1001/archneur.1964.00460160003001 · Cited by 1,930
Maruyama, M., Shimada, H., Suhara, T., Shinotoh, H., Ji, B., Maeda, J., Zhang, M.-R., Trojanowski, J. Q., Lee, V. M.-Y., Ono, M., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.037 · Cited by 760
Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges
Williams, D. R., & Lees, A. J. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70042-0 · Cited by 650
Self-citationSchneider, L., Olin, J. T., Doody, R. S., Clark, C. M., Morris, J. C., Reisberg, ., Schmitt, F. A., Grundman, M., Thomas, R. G., & Ferris, S. H. (1997) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199700112-00004 · Cited by 646
Self-citationA clinical rating scale for progressive supranuclear palsy
Golbe, L. I., & Ohman‐Strickland, P. (2007) · Brain · doi:10.1093/brain/awm032 · Cited by 628
Self-citationIdentification of common variants influencing risk of the tauopathy progressive supranuclear palsy
PSP Genetics Study Group, Höglinger, G. U., Melhem, N. M., Dickson, D. W., Sleiman, P. M. A., Wang, L.-S., Klei, L., Rademakers, R., de Silva, R., Litvan, I., et al. (2011) · Nature Genetics · doi:10.1038/ng.859 · Cited by 603
Self-citationHall, S., Öhrfelt, A., Constantinescu, R., Andreasson, U., Surova, Y., Bostrom, F., Nilsson, C., Widner, H., Decraemer, H., Nägga, K., et al. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.1654 · Cited by 473
Neuropathology of variants of progressive supranuclear palsy
Dickson, D. W., Ahmed, Z., Algom, A. A., Tsuboi, Y., & Josephs, K. A. (2010) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32833be924 · Cited by 386
Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: The NNIPPS Study
Bensimon, G., Ludolph, A., Agid, Y., Vidailhet, M., Payan, C., & Leigh, P. N. (2008) · Brain · doi:10.1093/brain/awn291 · Cited by 352
Self-citationAxonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab
Gunnarsson, M., Malmeström, C., Axelsson, M., Sundström, P., Dahle, C., Vrethem, M., Olsson, T. P., Piehl, F., Norgren, N., Rosengren, L., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22247 · Cited by 346
A phase 2 trial of the GSK‐3 inhibitor tideglusib in progressive supranuclear palsy
Tolosa, E., Litvan, I., Höglinger, G. U., Burn, D., Lees, A., Andrés, M. V., Gómez‐Carrillo, B., León, T., del Ser, T., & for the TAUROS Investigators (2014) · Movement Disorders · doi:10.1002/mds.25824 · Cited by 320
Self-citationCognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy
Brown, R. G., Lacomblez, L., Landwehrmeyer, G. B., Bak, T. H., Uttner, I., Dubois, B., Agid, Y., Ludolph, A. C., Bensimon, G., Payan, C., et al. (2010) · Brain · doi:10.1093/brain/awq158 · Cited by 317
Self-citationSchneider, L. S. S., Olin, J. T., Doody, R. S., Clark, C. M., Morris, J. C., Reisberg, ., Ferris, S. H., Schmitt, F. A., Grundman, M., & Thomas, R. G. (1997) · Birkhäuser Boston eBooks · doi:10.1007/978-1-4612-4116-4_64 · Cited by 300
Self-citationThe prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK
Nath, U. (2001) · Brain · doi:10.1093/brain/124.7.1438 · Cited by 256
Scherling, C. S., Hall, T., Berisha, F., Klepac, K., Karydas, A., Coppola, G., Kramer, J. H., Rabinovici, G., Ahlijanian, M., Miller, B. L., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24052 · Cited by 249
Self-citationZetterberg, H. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.90 · Cited by 234
Phenotypic correlations in FTDP-17.
Reed, L., Wszolek, Z., & Hutton, M. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00202-5 · Cited by 221
Paviour, D. C., Price, S. L., Jahanshahi, M., Lees, A. J., & Fox, N. C. (2006) · Brain · doi:10.1093/brain/awl021 · Cited by 217
Self-citationFagan, A. M., Shaw, L. M. J., Xiong, C., Vanderstichele, H., Mintun, M. A., Trojanowski, J. Q., Coart, E., Morris, J. C., & Holtzman, D. M. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.105 · Cited by 191
Rates of cerebral atrophy differ in different degenerative pathologies
Whitwell, J. L., Jack, C. R., Parisi, J. E., Knopman, D. S., Boeve, B. F., Petersen, R. C., Ferman, T. J., Dickson, D. W., & Josephs, K. A. (2006) · Brain · doi:10.1093/brain/awm021 · Cited by 174
Self-citationRandomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy
Litvan, I., Phipps, M., Pharr, V., Hallett, M., Grafman, J. H., & Salazar, A. (2001) · Neurology · doi:10.1212/wnl.57.3.467 · Cited by 164
Self-citationWorst-Rank Score Analysis with Informatively Missing Observations in Clinical Trials
Lachin, J. M. (1999) · Controlled Clinical Trials · doi:10.1016/s0197-2456(99)00022-7 · Cited by 164
Höglinger, G. U., Huppertz, H., Wagenpfeil, S., Andrés, M. V., Belloch, V., León, T., del Ser, T., & for the TAUROS MRI Investigators (2014) · Movement Disorders · doi:10.1002/mds.25815 · Cited by 161
Self-citationStamelou, M., Reuß, A., Pilatus, U., Magerkurth, J., Niklowitz, P., Eggert, K. M., Krisp, A., Menke, T., Schade‐Brittinger, C., Oertel, W. H., et al. (2008) · Movement Disorders · doi:10.1002/mds.22023 · Cited by 152
Self-citationNAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model
Shiryaev, N., Jouroukhin, Y., Giladi, E., Polyzoidou, E., Grigoriadis, N., Rosenmann, H., & Gozes, I. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.02.011 · Cited by 122
Self-citationMorimoto, B. H., Schmechel, D., Hirman, J., Blackwell, A., Keith, J., Gold, M., & on behalf of the AL-108-211 Study Investigators (2013) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000348347 · Cited by 115
Self-citationZolpidem in Progressive Supranuclear Palsy
Daniele, A., Moro, E., & Bentivoglio, A. R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908123410721 · Cited by 93
Rational therapeutic approaches to progressive supranuclear palsy
Stamelou, M., de Silva, R., Arias-Carrion, O., Boura, E., Hollerhage, M., Oertel, W. H., Muller, U., & Hoglinger, G. U. (2010) · Brain · doi:10.1093/brain/awq115 · Cited by 91
Self-citationPayan, C., Viallet, F., Landwehrmeyer, G. B., Bonnet, A.-M., Borg, M., Durif, F., Lacomblez, L., Bloch, F., Verny, M., Fermanian, J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022293 · Cited by 88
Self-citationIdazoxan treatment in progressive supranuclear palsy
Ghika, J. A., Tennis, M. K., Hoffman, E., Schoenfeld, D., & Growdon, J. H. (1991) · Neurology · doi:10.1212/wnl.41.7.986 · Cited by 74
Serial CSF sampling in Alzheimer's disease: specific versus non-specific markers
Kester, M. I., Scheffer, P. G., Simmelink, M. J. A., Twaalfhoven, H. A. M., Verwey, N. A., Veerhuis, R., Twisk, J. W. R., Bouwman, F. H., Blankenstein, M. A., Scheltens, P., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.05.013 · Cited by 63
Treatment of progressive supranuclear palsy with tricyclic antidepressants
Newman, G. C. (1985) · Neurology · doi:10.1212/wnl.35.8.1189 · Cited by 57
Boxer, A. L., Gold, M., Huey, E. D., Hu, W. T., Rosen, H. J., Kramer, J. H., Gao, F., Burton, E. A., Chow, T. W., Kao, A. W., et al. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.03.003 · Cited by 55
Self-citationControlled trial of pergolide mesylate in Parkinson's disease and progressive supranuclear palsy
Jankovic, J. J. (1983) · Neurology · doi:10.1212/wnl.33.4.505 · Cited by 49
Physostigmine treatment of progressive supranuclear palsy
Litvan, I., Med, C. G., Atack, J. R., Gillespie, M., Kask, A. M., Mouradian, M. M., & Chase, T. N. (1989) · Annals of Neurology · doi:10.1002/ana.410260318 · Cited by 47
Self-citationRandomization-based nonparametric methods for the analysis of multicentre trials
LaVange, L. M., Durham, T. A., & Koch, G. G. (2005) · Statistical Methods in Medical Research · doi:10.1191/0962280205sm397oa · Cited by 47
Modeling trajectories of regional volume loss in progressive supranuclear palsy
Josephs, K. A., Xia, R., Mandrekar, J. N., Gunter, J. L., Senjem, M. L., Jack, C. R., & Whitwell, J. L. (2013) · Movement Disorders · doi:10.1002/mds.25437 · Cited by 45
Self-citationFoster, N. L., Aldrich, M. S., Bluemlein, L., White, R. F., & Berent, S. (1989) · Neurology · doi:10.1212/wnl.39.2.257 · Cited by 44
Frattali, C., Sonies, B. C., Chi‐Fishman, G., & Litvan, I. (1999) · Dysphagia · doi:10.1007/pl00009600 · Cited by 40
Self-citationEfaroxan, an alpha‐2 antagonist, in the treatment of progressive supranuclear palsy
Rascol, O., Sieradzan, K., Peyro-Saint-Paul, H., Thalamas, C., Brefel‐Courbon, C., Sénard, J., Ladure, P., Montastruc, J. L., & Lees, A. J. (1998) · Movement Disorders · doi:10.1002/mds.870130411 · Cited by 35
Self-citationPoujois, A., Vidailhet, M., Trocello, J., Bourdain, F., Gaymard, B. M., & Rivaud-Péchoux, S. (2007) · European Journal of Neurology · doi:10.1111/j.1468-1331.2007.01687.x · Cited by 18
Cited by
Sorted by citations
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251
Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113
DeVos, S. L., Miller, R. L., Schoch, K. M., Holmes, B. B., Kebodeaux, C. S., Wegener, A. J., Chen, G., Shen, T., Tran, H., Nichols, B., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aag0481 · Cited by 516
Boxer, A. L., Yu, J.-T., Golbe, L. I., Litvan, I., Lang, A. E., & Höglinger, G. U. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30157-6 · Cited by 485
Self-citationO'Brien, J. T., Holmes, C., Jones, M. S., Jones, R. W., Livingston, G., McKeith, I. G., Mittler, P. J., Passmore, P., Ritchie, C. W., Robinson, L. A., et al. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881116680924 · Cited by 361
Metadata
- Authors
- Boxer, A. L., Lang, A. E., Grossman, M., Knopman, D. S., Miller, B. L., Schneider, L. S., Doody, R. S., Lees, A., Golbe, L. I., Williams, D. R., Corvol, J.-C., Ludolph, A., Burn, D., Lorenzl, S., Litvan, I., Roberson, E. D., Höglinger, G. U., Koestler, M., Jack, C. R., Van Deerlin, V., Randolph, C., Lobach, I. V., Heuer, H. W., Gozes, I., Parker, L., Whitaker, S., Hirman, J., Stewart, A. J., Gold, M., & Morimoto, B. H.
- Affiliations
- University of California, San Francisco (US)
- University of Toronto (CA)
- University of Pennsylvania (US)
- Mayo Clinic (US)
- University of Southern California (US)
- Baylor College of Medicine (US)
- UCL Queen Square Institute of Neurology (GB)
- Rutgers, The State University of New Jersey (US)
- Monash University (AU)
- University Hospital Ulm (DE)
- Newcastle University (GB)
- LMU Klinikum (DE)
- University of California San Diego (US)
- University of Alabama at Birmingham (US)
- Technical University of Munich (DE)
- Loyola University Chicago (US)
- Tel Aviv University (IL)
- Arbutus Biopharma (Canada) (CA)
- Omeros Corporation (United States) (US)
- Paladin Labs (Canada) (CA)
- Celerion (United States) (US)
- Corresponding author
- Boxer, Adam L
- ORCID
- Boxer, Adam L
- Lang, Anthony E
- Grossman, Murray
- Knopman, David S
- Miller, Bruce L
- Schneider, Lon S
- Lees, Andrew
- Golbe, Lawrence I
- Williams, David R
- Burn, David
- Lorenzl, Stefan
- Litvan, Irene
- Roberson, Erik D
- Höglinger, Günter U
- Jack, Clifford R
- Randolph, Christopher
- Lobach, Iryna V
- Heuer, Hilary W
- Gozes, Illana
- Stewart, Alistair J
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 13
- Issue
- 7
- Pages
- 676-685
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC4129545
- OpenAlex
- W2129669150
- Cited by
- 294
- References
- 43
- Citations by year
- 2026: 21 · 2025: 18 · 2024: 15 · 2023: 22 · 2022: 16 · 2021: 25 · 2020: 27 · 2019: 33 · 2018: 23 · 2017: 27 · 2016: 36 · 2015: 20 · 2014: 10
- FWCI
- 20.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Allos Therapeutics
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Keywords
- davunetide, progressive supranuclear palsy, tau pathology, microtubule stabilization, tau phosphorylation, intranasal drug delivery, neuroprotection, PSP Rating Scale, activities of daily living, drug safety, epistaxis, serious adverse events, atypical parkinsonism, disease-modifying therapy
- MeSH terms
- Aged, Double-Blind Method, Female, Humans, Male, Oligopeptides, Supranuclear Palsy, Progressive, Treatment Outcome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
