Evidence map›Paper›PMID 32468646›Full record

ArticleAnnals of neurology2020

Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer's Disease.

Raymond S Turner, Michaeline L Hebron, Abigail Lawler, Elizabeth E Mundel, Nadia Yusuf, J Nathan Starr, Muhammad Anjum, Fernando Pagan, Yasar Torres-Yaghi, Wangke Shi and 9 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05143528 (A Multicenter, Phase III, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Nilotinib BE in Subjects With Early Alzheimer's Disease), which is not on this map. Cited by 78 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 2 pooled it
7.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05143528 phase3unknown statusnot on this mapstarted 2022, after this paper: background citation

A Multicenter, Phase III, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Nilotinib BE in Subjects With Early Alzheimer's Disease (NILEAD)

TypeinterventionalSponsorKeifeRx, LLCRan2022 to 2026Enrolled1,275ConditionsAlzheimer DiseaseArmsNilotinib BE 84mg, Nilotinib BE 112 mg, Placebo
3 · Its place in the literature

Who cites it

78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 122 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Long-Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021
    Trial
  5. Article
  6. Tyrosine kinase inhibitor use and risk of neurodegenerative disease: A Swedish population-based cohort study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. New Approaches to the Treatment of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025
    Review
  19. Review
  20. Article

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 1 country.

Raymond S TurnerMemory Disorders Program, Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
Michaeline L HebronTranslational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
Abigail LawlerMovement Disorders Clinic, Department of Neurology, MedStar Georgetown University Hospital, Washington, DC, USA.
Elizabeth E MundelMovement Disorders Clinic, Department of Neurology, MedStar Georgetown University Hospital, Washington, DC, USA.
Nadia YusufMovement Disorders Clinic, Department of Neurology, MedStar Georgetown University Hospital, Washington, DC, USA.
J Nathan StarrMovement Disorders Clinic, Department of Neurology, MedStar Georgetown University Hospital, Washington, DC, USA.
Muhammad AnjumMovement Disorders Clinic, Department of Neurology, MedStar Georgetown University Hospital, Washington, DC, USA.
Fernando PaganMovement Disorders Clinic, Department of Neurology, MedStar Georgetown University Hospital, Washington, DC, USA.
Yasar Torres-YaghiMovement Disorders Clinic, Department of Neurology, MedStar Georgetown University Hospital, Washington, DC, USA.
Wangke ShiTranslational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
Sanjana MulkiTranslational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
Dalila FerranteTranslational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
Sara MatarTranslational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
Xiaoguang LiuTranslational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
Giuseppe EspositoDivision of Nuclear Medicine, Washington, DC, USA.
Frank BerkowitzDepartment of Radiology, MedStar Georgetown Hospital, Washington, DC, USA.
Xiong JiangDepartment of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.ORCID 0000-0001-7054-1556
Jaeil AhnDepartment of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, DC, USA.
Charbel MoussaTranslational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.ORCID 0000-0002-2012-7063
Georgetown University · USMedStar Georgetown University Hospital · USMedStar Washington Hospital Center · US

Funding

Georgetown-Howard Universities Center for Clinical and Translational Science (GHUUL1TR000101 · NCATS · GEORGETOWN UNIVERSITY · PI MELLMAN, THOMAS A, VERBALIS, JOSEPH G · 2012 to 2015
$19.3M
Georgetown-Howard Universities Center for Clinical and Translational Science (GHUUL1RR031975 · NCRR · GEORGETOWN UNIVERSITY · PI VERBALIS, JOSEPH G · 2010 to 2011
$14.6M
NCATS NIH HHS UL1 TR000101NCRR NIH HHS UL1 RR031975
6 · The paper itself

Abstract

objectivePreclinical evidence with nilotinib, a US Food and Drug Administration (FDA)-approved drug for leukemia, indicates improvement in Alzheimer's disease phenotypes. We investigated whether nilotinib is safe, and detectable in cerebrospinal fluid, and alters biomarkers and clinical decline in Alzheimer's disease.

methodsThis single-center, phase 2, randomized, double-blind, placebo-controlled study investigated the safety, tolerability, and pharmacokinetics of nilotinib, and measured biomarkers in participants with mild to moderate dementia due to Alzheimer's disease. The diagnosis was supported by cerebrospinal fluid or amyloid positron emission tomography biomarkers. Nilotinib 150 mg versus matching placebo was taken orally once daily for 26 weeks followed by nilotinib 300 mg versus placebo for another 26 weeks.

resultsOf the 37 individuals enrolled, 27 were women and the mean (SD) age was 70.7 (6.48) years. Nilotinib was well-tolerated, although more adverse events, particularly mood swings, were noted with the 300 mg dose. In the nilotinib group, central nervous system (CNS) amyloid burden was significantly reduced in the frontal lobe compared to the placebo group. Cerebrospinal fluid Aβ40 was reduced at 6 months and Aβ42 was reduced at 12 months in the nilotinib group compared to the placebo. Hippocampal volume loss was attenuated (-27%) at 12 months and phospho-tau-181 was reduced at 6 months and 12 months in the nilotinib group.

interpretationNilotinib is safe and achieves pharmacologically relevant cerebrospinal fluid concentrations. Biomarkers of disease were altered in response to nilotinib treatment. These data support a larger, longer, multicenter study to determine the safety and efficacy of nilotinib in Alzheimer's disease. ANN NEUROL 2020 ANN NEUROL 2020;88:183-194.

Indexed as

AgedAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersBrainDouble-Blind MethodFemaleHumansMaleMiddle AgedPeptide FragmentsPositron-Emission TomographyProtein-Tyrosine KinasesPyrimidinestau ProteinsTreatment OutcomeAmyloid beta-PeptidesBiomarkersnilotinibPeptide FragmentsProtein-Tyrosine KinasesPyrimidinestau Proteins

Identifiers

PMID32468646
PMCPMC7383852
OpenAlexW3030228225

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.