We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Safety, target engagement, and biomarker effects of bosutinib in dementia with Lewy bodies.
- Authors
Pagan, Fernando L.; Torres-Yaghi, Yasar; Hebron, Michaeline L.; Wilmarth, Barbara; Turner, R. Scott; Matar, Sara; Ferrante, Dalila; Ahn, Jaeil; Moussa, Charbel
- Abstract
Introduction: Bosutinib, a dual Abelson/Src inhibitor, was investigated in individuals with dementia with Lewy bodies (DLB). Methods: A single site, randomized, double-blind, placebo-controlled study of the effects of oral bosutinib, 100 mg once daily for 12 weeks on primary safety and pharmacokinetics and secondary biomarker outcomes. Results: Twenty-six participants were randomized and includedmale and female (12:1) in the bosutinib arm and all male (13) in the placebo arm. The average age was 72.9 ± 8.1 (year±standard deviation). Therewere no serious adverse events and no dropouts. Bosutinib was measured in the cerebrospinal fluid (CSF) and inhibited Abelson. Bosutinib reduced CSF alpha-synuclein and dopamine catabolism. Discussion: Bosutinib is safe and well tolerated and penetrates the blood-brain barrier to inhibit Abelson and reduce CSF alpha-synuclein and dopamine catabolism, suggesting that bosutinib (100 mg) may be at or near the lowest effective dose in DLB. These resultswill guide adequately powered studies to determine the efficacy of a dose range of bosutinib and longer treatment in DLB.
- Subjects
LEWY body dementia; BIOMARKERS; BLOOD-brain barrier; CEREBROSPINAL fluid; ALPHA-synuclein; DOPAMINE
- Publication
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2022, Vol 8, Issue 1, p1
- ISSN
2352-8737
- Publication type
Article
- DOI
10.1002/trc2.12296