Scientists have advanced a phase 1 clinical trial exploring an oral treatment that combines quercetin and dasatinib for individuals showing early, symptomatic signs of Alzheimer’s disease. The study was published in Nature Medicine, signaling a first look at the safety and potential signals of efficacy for this senolytic approach in humans.
In aging biology, cells sometimes enter a state where they do not die but stop functioning normally. These senescent cells release a mix of substances that can disrupt neighboring cells and promote local inflammation, contributing to cognitive decline. Senolytic molecules aim to clear these dysfunctional cells, but until now, clinical trials have not demonstrated a clear, consistent benefit in humans.
The trial enrolled five participants aged 65 and older who exhibited early Alzheimer’s disease symptoms. Over a 12-week period, they received multiple cycles of senolytic therapy. Across 11 clinical visits, participants underwent thorough physical examinations, laboratory assessments, and cognitive testing using the Montreal Cognitive Assessment to measure changes in mental function.
Researchers found that dasatinib crossed the blood brain barrier and reached the central nervous system in the treated individuals. The twice-weekly dosing schedule was associated with a 35 percent reduction in the accumulation of neurofibrillary tangles in the brain. This decrease aligned with slower patterns of cortical atrophy and improved regional cerebral blood flow. Neurofibrillary tangles are a defining pathology of Alzheimer’s disease and are closely linked to neuronal damage and disease progression.
Overall tolerability was favorable, with no serious adverse events reported. Cognitive performance and brain imaging at the end of the treatment period were similar to baseline measurements, providing early evidence that the regimen is safe in this small cohort. The researchers emphasize that larger, longer trials are necessary to better characterize potential benefits, optimize dosing, and determine the best treatment duration for sustained effects.
These initial results contribute to a growing body of work on senolytics as a strategy to modify disease processes in aging and neurodegeneration. While the data are preliminary, they offer a foundation for future studies that could clarify which patients may derive the most benefit and how best to combine quercetin with dasatinib to achieve durable outcomes. Ongoing work aims to refine biomarkers, monitor long-term safety, and establish standardized regimens that could be tested in broader populations in Canada and the United States.
Remarkable questions remain about translating these findings into routine care, including how to identify ideal candidates, manage potential side effects over longer periods, and determine the precise impact on cognitive trajectories. Still, the study marks an important step forward in exploring how clearing harmful senescent cells might alter the course of Alzheimer’s disease and related cognitive disorders, offering a glimmer of hope for patients, families, and clinicians seeking new avenues beyond current therapies.
The study and its early observations are reported in Nature Medicine for researchers and health professionals seeking to understand the evolving landscape of senolytic interventions in neurodegenerative disease.