title: Nilotinib Effects in Parkinson's disease and Dementia with Lewy bodies.
abstract: We evaluated the effects of low doses of the tyrosine kinase Abelson (Abl) inhibitor Nilotinib, on safety and pharmacokinetics in Parkinson's disease dementia or dementia with Lewy bodies.
  
  
  
  The primary outcomes of this study were safety and tolerability; pharmacokinetics and target engagement were secondary, while clinical outcomes were exploratory.
  
  
  
  Twelve subjects were randomized into 150 mg (n = 5) or 300 mg (n = 7) groups and received Nilotinib orally every day for 24 weeks.
  
  
  
  This study shows that 150 mg and 300 mg doses of Nilotinib appear to be safe and tolerated in subjects with advanced Parkinson's disease. Nilotinib is detectable in the cerebrospinal fluid (CSF) and seems to engage the target Abl. Motor and cognitive outcomes suggest a possible beneficial effect on clinical outcomes. The CSF levels of homovanillic acid are significantly increased between baseline and 24 weeks of treatment. Exploratory CSF biomarkers were measured.
  
  
  
  This small proof-of-concept study lacks a placebo group and participants were not homogenous, resulting in baseline differences between and within groups. This limits the interpretations of the biomarker and clinical data, and any conclusions should be drawn cautiously. Nonetheless, the collective observations suggest that it is warranted to evaluate the safety and efficacy of Nilotinib in larger randomized, double-blind, placebo-controlled trials.
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pagan
authors.affiliation: Department of Neurology, Laboratory for Dementia and Parkinsonism, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Michaeline
authors.initials: M
authors.lastname: Hebron
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Ellen H
authors.initials: EH
authors.lastname: Valadez
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Yasar
authors.initials: Y
authors.lastname: Torres-Yaghi
authors.affiliation: Department of Neurology, Laboratory for Dementia and Parkinsonism, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Reversa R
authors.initials: RR
authors.lastname: Mills
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Wilmarth
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Hellen
authors.initials: H
authors.lastname: Howard
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Connell
authors.initials: C
authors.lastname: Dunn
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Carlson
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Lawler
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Sean L
authors.initials: SL
authors.lastname: Rogers
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Ramsey A
authors.initials: RA
authors.lastname: Falconer
authors.affiliation: Department of Biostatistics, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Jaeil
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurology, Laboratory for Dementia and Parkinsonism, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Georgetown University Medical Center, Washington, DC, USA.|Department of Neurology, National Parkinson's Foundation Center for Excellence, Translational Neurotherapeutics Program. Movement Disorders Program. MedStar Georgetown Hospital Washington, DC, USA.
authors.forename: Charbel
authors.initials: C
authors.lastname: Moussa
mesh_terms: D003704:Dementia / Q000188:drug therapy* / Q000209:etiology; D005500:Follow-Up Studies; D006801:Humans; D020961:Lewy Body Disease / Q000188:drug therapy; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D011743:Pyrimidines; C498826:nilotinib
keywords: Lewy bodies; Nilotinib; Parkinson; dopamine; homovanillic acid; synuclein; tau