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CTAD 2022 | The impact of TKIs on miRNA expression in the treatment of AD

Charbel Moussa, MBBS, PhD, Georgetown University Medical Center, Washington, D.C., discusses the impact of tyrosine kinase inhibitor (TKI) use on microRNA (miRNA) expression in Alzheimer’s disease (AD). Looking at miRNAs is useful because they are very stable molecules and they inversely regulate the expression of mRNA which translates into proteins. In AD, Parkinson’s, and Dementia with Lewy bodies, researchers have been carrying out cerebrospinal fluid (CSF) miRNA profiling using whole genome sequencing. CSF samples collected from over 300 patients at baseline and at the end of treatment have not only shown that miRNAs are very highly stable, but also that the entire miRNA genome can be detected in these samples. Whole genome expression analyses of miRNAs was used in clinical studies of the tyrosine kinase inhibitor, nilotinib. Several actions of nilotinib on miRNAs have been observed: it affects miRNAs that control gene expression of autophagy, inflammation and blood-brain barrier integrity. Facilitation of autophagy, modulation of inflammation, and protection of the blood-brain barrier are all effects that have been seen when using nilotininb in preclinical animal models, matching the changes in miRNAs seen in patients with AD. This interview took place at the Clinical Trials on Alzheimer’s Disease congress 2022 in San Francisco.

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