Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients

We explored the effects of a low dose of nilotinib (150 mg) on behavioral changes and motor symptoms in manifest HD patients and examined the effects of nilotinib on several brain mechanisms, including dopamine transmission and gene expression via cerebrospinal fluid (CSF) miRNA sequencing. Nilotinib, 150 mg, did not result in any behavioral changes, although it significantly attenuated HVA levels, suggesting reduction of dopamine catabolism. There was no significant change in HTT, phosphorylated neuro-filament and inflammatory markers in the CSF and plasma via immunoassays. Whole miRNA genome sequencing of the CSF revealed significant longitudinal changes in miRNAs that control specific genes associated with autophagy, inflammation, microglial activity and basal ganglia neurotransmitters, including dopamine and serotonin. Overall design: We performed whole genome miRNA sequencing in the CSF (n = 5) collected at baseline and 3 months from each individual patient to allow us to measure longitudinal miRNA changes. miRNAs inversely regulate mRNA, and they do not necessarily require large changes to affect their targets, therefore, we assessed all miRNA that met p < 0.05 between 3 months and baseline