BCR-ABL Tyrosine Kinase Inhibitors in Parkinson's Disease and Lewy Body Dementia: A Systematic Review
Giovanni Berton1, Amanda Lima2, Rafael Borges3, Nicole Cardoso4, Marcos Marques5, Thiago Oliveira6
1Medical School, University of Passo Fundo, 2Universidade Positivo, 3Federal University of Minas Gerais - Medical School, 4Faculdade Santa Marcelina, 5Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 6Universidade Federal de Minas Gerais
Objective:
To assess the effect of BCR-ABL Tyrosine Kinase Inhibitors (TKI) on Parkinson's Disease (PD) and Lewy Body Dementia (LBD).
Background:
Abelson tyrosine kinase activation is higher in PD. Inhibiting its activation could be a disease-modifying therapy.
Design/Methods:
On a systematic review of MEDLINE, Embase, and Cochrane, 427 papers were selected after deduplication. RCTs and Non-RCTs on BCR-ABL TKI in PD and LBD were included using a PRISMA protocol. After full-text screening, 6 articles remained.
Results:
189 patients were randomized into 2 groups: BCR-ABL TKI vs Levodopa equivalent daily dose. Pagan et al., 2016 analyzed Nilotinib in PD and LBD with an average decrease of 3.4 and 3.6 points on the UPDRS-III, and 7 and 11.1 in the UPDRS I-IV score with 150 and 300 mg, respectively. Simuni et al., 2020 evaluated 76 patients for both doses of Nilotinib in moderately advanced PD; the results showed no difference in MDS-UPDRS-III OFF and a worsening in MDS-UPDRS-III ON. Pagan et al., 2019 randomized 75 patients into both doses of Nilotinib, resulting in a 2.82 points reduction in the MDS-UPDRS-III for Nilotinib 150 mg. MDS-UPDRS I-III and MDS-UPDRS I-IV scores increased by 2.47 and 2.13 points in the placebo group but remained stable in the Nilotinib groups. Pagan et al., 2021 randomized 63 of the same patients for Nilotinib 150 vs 300 mg, suggesting that Nilotinib 300 mg maintained stability for 27 months while Nilotinib 150 mg did not. Pagan et al., 2022 randomized 26 patients for Busotinib in LBD with no impact in UPDRS I, II, or III. Also, Watson-Fargie et al., 2018 reported in a review of 2 cases that Imatinib could reduce UPDRS-III progression in PD.
Conclusions:
Reviewed data suggests possible stabilization but no solid clinical improvement. Larger-sample trials might bring further information on all 3 drugs and BCR-ABL TKI in general.