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CTAD 2022 | Nilotinib: a potential repurposed treatment for Alzheimer’s disease?

Charbel Moussa, MBBS, PhD, Georgetown University Medical Center, Washington, D.C., discusses the potential use of nilotinib as a treatment for Alzheimer’s disease (AD). Nilotinib belongs to a family of drugs called tyrosine kinase inhibitors (TKIs), which have been widely used in cancer treatment, particularly leukemia. Nilotinib inhibits the ABL gene which can mutate and causes chronic myelogenous leukemia. This drug has been used clinically for 15 years and is FDA- and EMA-approved. Although, nilotinib has a much higher specificity to another tyrosine kinase called discodin domain receptor (DDR), which is involved in the facilitation of autophagy and modulation of inflammation and vascular tissue around the body. It was found in several post-mortem studies that DDR is overexpressed in many neurodegenerative diseases, therefore, researchers rationalized that using nilotinib would inhibit DDR1, trigger autophagy, trigger an anti-inflammatory response, and induce repair of the blood-brain barrier. Nilotinib BE, which is currently being investigated in the AD space, is a bioequivalent which is used at a lower dose and has demonstrated better solubility and bioavailability in fasted and fed AD patients. This interview took place at the Clinical Trials on Alzheimer’s Disease congress 2022 in San Francisco.