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CTAD 2022 | The potential of nilotinib in the treatment of movement disorders

Nilotinib is a cellular Abelson (c-Abl) tyrosine kinase and discoidin domain receptor (DDR) inhibitor that is most well known for its use in treating chronic myeloid leukemia (CML). Post-mortem studies showed that DDRs are overexpressed in the midbrain of patients with PD, suggesting its association with PD progression. Subsequent studies in several models of neurodegeneration demonstrated that treatment with nilotinib could increase dopamine levels and decrease ɑ-synuclein and hyper-phosphorylated tau (p-tau). These findings sparked interest into the clinical effects of nilotinib to treat movement disorders such as PD. Charbel Moussa, MBBS, PhD, Georgetown University Medical Center, Washington, D.C., outlines some of the results from the Phase II clinical trial, NILO-PD (NCT03205488), that concluded that nilotinib was safe and well-tolerated in 76 patients with PD, but showed poor central nervous system penetration and failed to show changes in the levels of dopamine or its metabolites. Dr Moussa suggests that the next steps would be to either investigate the effects of nilotinib in levodopa-naive patients at an earlier stage of PD or to treat patients with nilotinib on top of levodopa for a longer period of time (≥2 years). This interview took place at the Clinical Trials on Alzheimer’s Disease congress 2022 in San Francisco.

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