Nilotinib in Parkinson's disease: A systematic review and meta-analysis

Abstract

BackgroundNilotinib, which inhibits cellular Abelson tyrosine kinase, may be an effective treatment for patients with Parkinson's disease (PD). The purpose of this study is to evaluate the outcomes of different doses of nilotinib in patients with PD.MethodsWe searched PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Clinical Trials from inception to 7 March 2022 to identify all randomized controlled trials (RCTs) of nilotinib reporting outcomes of interest in patients with PD. Outcomes included tolerability, efficacy, safety, and CSF biomarker levels. Review manager 5.4 software was used to analyze all data.ResultsThree RCTs with a total of 163 patients were included. No significant difference was found between 150 mg nilotinib or 300 mg nilotinib and placebo in terms of tolerability, adverse events, or HVA levels. 300 mg nilotinib showed significantly higher Movement Disorder Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) scores [SMD = 0.52, 95%CI = (0.12, 0.92), P = 0.01] and 3,4-dihydroxyphenylacetic acid (DOPAC) levels [SMD = 0.52, 95%CI = (0.12, 0.92), P = 0.01], and lower α-synuclein levels [SMD = −2.16, 95%CI = (−3.38, −1.84), P < 0.00001] compared with placebo. And compared with 150 mg nilotinib, 300 mg nilotinib showed significantly lower α-synuclein levels [SMD = −1.16, 95%CI = (−1.70, −0.61), P < 0.0001].ConclusionsAlthough our study demonstrated favorable tolerability and safety of different doses of nilotinib, and improvement in part of CSF biomarker levels of 300 mg nilotinib, the poor efficacy on motor outcomes indicated that nilotinib had no advantages in the clinic.

Therapeutic Monitoring of Orally Administered, Small-Molecule Anticancer Medications with Tumor-Specific Cellular Protein Targets in Peripheral Fluid Spaces—A Review

“…It is increasingly acknowledged that certain OACDs may be effective against neurodegenerative and autoimmune diseases [ 9 , 108 ]. Nilotinib, a BCR-ABL tyrosine kinase inhibitor, has been investigated in multiple cases as a medication against mental disorders, such as Parkinson’s disease and Alzheimer’s disease [ 109 , 110 ]. The rationale of these indications is that nilotinib leads to the degradation of misfolded α-synuclein by autophagy [ 111 ].…”

Pathogenic Aspects and Therapeutic Avenues of Autophagy in Parkinson’s Disease

“…Tested on clinical phase I and phase II studies, it proves its safety and tolerability, with no adverse effects observed and a decrease in oligomeric forms of the α-syn in PD patients [198,199]. However, a recent meta-analysis concluded that it had no effect on motor outcomes [200]. Pagan and colleagues support starting a phase 3 trial project to evaluate nilotinib 300 mg in a more extensive multicenter study [199].…”

MRI-based Differentiation of Parkinson's Disease by Cerebellar Gray Matter Volume

“…A meta-analysis of fMRI research on cognitively impaired PD patients indicates that cognitive dysfunction in PD is related to decreased connectivity within cognitive-related networks, with the most prominent effect observed in the default mode network (DMN) [31]. Another fMRI meta-analysis revealed a series of brain perfusion and regional functional abnormalities in PD, which are predominantly centered around brain regions related to the striato-thalamo-cortical circuits, are associated with the clinical manifestations of patients with PD [32]. MRI-based assessment of brain gray matter volume is considered as an effective method to diagnose PD and to evaluate its progression.…”