Encouraging results from a small Phase 2 human trial testing the effects of a cancer drug in treating Alzheimer’s disease have been published in the journal Annals of Neurology. The data suggests the drug is safe, well-tolerated and alters biomarkers associated with Alzheimer’s. A larger efficacy study is currently planned.
Nilotinib (brand name Tasigna) is an oral medication, originally developed to treat leukemia and approved for medical use in the United States by the FDA in 2007. The drug works by inhibiting a key protein involved in cell growth and animal studies have demonstrated it can effectively cross the blood-brain barrier and possibly disrupt the aggregation of toxic proteins associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
Early human trials testing nilotinib for the treatment of Parkinson’s disease have delivered mixed results. Two recently published small Phase 2 trials reported conflicting data, and some experts expressed concern over whether the drug has any potential in producing clinically meaningful outcomes for Parkinson’s patients.
The first data from trials testing the drug for Alzheimer’s suggests promising potential, although it is certainly too early to know whether the treatment is clinically efficacious. R. Scott Turner, principal investigator on this new study from Georgetown University Medical Center, points out the goal of this initial trial was only to establish safety, tolerability and the pharmacokinetics of nilotinib in Alzheimer’s disease patients.
"The primary goal of this study was to determine its safety and tolerability in Alzheimer's patients," says Turner. "The study found that it is safe and well-tolerated, as we anticipated, and that it may have disease modifying benefits."
A small cohort of 37 Alzheimer’s patients with mild cognitive impairment were randomly, and blindly, assigned either a placebo or nilotinib for 12 months. Halfway through the year-long trial, the active drug group shifted to a higher dose, to better investigate the treatment’s safety profile.
The most prominent adverse effect seen in the trial was mood swings, only noted when subjects moved to the higher dose. The purpose of the study wasn't to determine whether the treatment improves, or slows, cognitive decline. However, toxic protein biomarkers in spinal fluid were altered in the drug cohort, compared to placebo, suggesting the treatment should progress to larger efficacy trials.
"The current data are in agreement with previous preclinical and other clinical studies at Georgetown suggesting nilotinib is a potential disease-modifying drug that triggers autophagy of neurotoxic proteins including Aβ40/, Aβ42, and phospho tau-181," explains Charnel Moussa, senior author on the study and director of the Georgetown Translational Neurotherapeutics Program. "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 study.”
It is still early days, and Alzheimer’s research is particularly notorious in delivering promising early-stage data only to fail in later-stage trialing. But, these initial results are encouraging, and they deliver the first clinical trial data demonstrating an oral treatment reducing the burden of toxic proteins in the brains of Alzheimer’s patients.
The new study was published in the journal Annals of Neurology.
