In a new study, researchers found that low doses of cancer drug nilotinib may help treat people with Alzheimer’s disease.
They found that it is safe and well-tolerated and suggested the drug should be tested in a larger study to further determine its safety and efficacy
The research was conducted by a team at Georgetown University.
Nilotinib is approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic myeloid leukemia.
The rationale for studying nilotinib in Alzheimer’s disease is based on previous research conducted by the team.
Nilotinib appears to aid in the clearance of accumulated beta-amyloid (Abeta) plaques and Tau tangles in neurons in the brain — hallmarks of Alzheimer’s disease.
It may penetrate the blood-brain barrier and turn on the “garbage disposal” machinery inside neurons (a process known as autophagy) to get rid of the Tau, Abeta, and other toxic proteins.
The primary goal of this study was to determine its safety and tolerability in Alzheimer’s patients.
After careful screening, 37 people with mild dementia due to Alzheimer’s were randomized to either the placebo or nilotinib groups for the 12-month study.
A 150 mg daily dose of nilotinib or matching placebo was taken orally once daily for 26 weeks followed by a 300 mg daily dose of nilotinib or placebo for another 26 weeks.
The team found nilotinib was safe and well-tolerated, although more adverse events, particularly mood swings (agitation and irritation), were noted at the 300 mg dose.
Mood swings were strongly increased between 6 and 12 months after the dose was increased from 150 mg to 300 mg daily.
Nilotinib carries an FDA “black-box warning” because of heart issues that may lead to sudden death in cancer patients (typically treated with 600 mg daily), but no such incidents occurred in this study (maximum dose of 300 mg daily).
The amyloid burden as measured by brain imaging was reduced in the nilotinib group compared to the placebo group.
Two forms of amyloid in cerebrospinal fluid were also measured. Aβ40 was reduced at 6 months and Aβ42 was reduced at 12 months in the nilotinib group compared to placebo.
Hippocampal volume loss (on MRI scans of the brain) was attenuated at 12 months and phospho-tau-181 in spinal fluid was reduced at 6 and 12 months in the nilotinib treated group.
The findings show that nilotinib is a potential disease-modifying drug that triggers autophagy of neurotoxic proteins including Aβ40/, Aβ42, and phospho tau-181.
The increase in mood swings with 300 mg nilotinib is associated with dose-dependent increases of brain dopamine, suggesting that 150 mg nilotinib is the optimal dosage to investigate in a future Alzheimer’s study.
This is the first oral treatment found to lower amyloid burden in the brain. Future Alzheimer’s studies are now in the planning stage.
One author of the study is Scott Turner, PhD, MD, director of Georgetown’s Memory Disorders Program.
The study is published in the Annals of Neurology.
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