ALSENLITE: Senolytics Trial for Alzheimer's Disease (NCT04785300)
Overview
Mermaid diagram (expand to render)
ALSENLITE is a Phase 1/2 clinical trial evaluating the senolytic drug combination of Dasatinib and Quercetin for the treatment of mild-to-moderate Alzheimer's disease (AD). This groundbreaking trial, conducted at the Mayo Clinic, represents one of the first clinical investigations of senolytic therapy in neurodegenerative disease. The study aims to evaluate whether clearing senescent cells from the brain can reduce neuroinflammation and potentially slow disease progression["@kirkland2022"][@passos2020].
Trial Details
| Attribute | Value | |-----------|-------| | NCT Number | NCT04785300 | | Phase | Phase 1/2 | | Status | Completed | | Sponsor | Mayo Clinic | | Intervention | Dasatinib + Quercetin (D+Q) | | Participants | 20 patients with mild-to-moderate AD | | Duration | 12 weeks treatment with 6-month follow-up | | ClinicalTrials.gov | [View Trial](https://clinicaltrials.gov/study/NCT04785300) |
Mechanism of Action
Senolytic Strategy
The ALSENLITE trial is based on the senolytic hypothesis—a therapeutic approach that targets and eliminates senescent cells that accumulate with aging and contribute to chronic inflammation[@baker2016].
Dasatinib + Quercetin Combination
The drug combination used in this trial works through complementary mechanisms:
Dasatinib: A tyrosine kinase inhibitor originally approved for chronic myeloid leukemia. It inhibits src family kinases and other pathways involved in senescent cell survival[@sharpless2017].
Quercetin: A natural flavonoid with broad senolytic activity. It targets multiple pro-survival pathways in senescent cells including PI3K, AKT, and BCL-2 family proteins[@zhu2015].
The combination is abbreviated as D+Q and has been shown in preclinical studies to reduce senescent cell burden in various tissues including brain tissue.
Connection to Neuroinflammation
Senescent cells secrete a pro-inflammatory cocktail known as the Senescence-Associated Secretory Phenotype (SASP). In the aging brain and in AD, these SASP factors contribute to:
Chronic neuroinflammation
Neuronal dysfunction and loss
Dysfunction of supporting glial cells
Tau pathology acceleration
By eliminating senescent cells, senolytic therapy aims to reduce the SASP burden and thereby mitigate neuroinflammation—a key driver of neurodegenerative processes in Alzheimer's disease[@baker2022][@ogrodnik2019].
Study Design
Eligibility Criteria
Inclusion Criteria:
Age 55-80 years
Clinical diagnosis of mild-to-moderate Alzheimer's disease
MMSE score between 16-26
Stable AD medication regimen
Consent from caregiver/guardian
Exclusion Criteria:
Significant cardiovascular disease
Active cancer or history of cancer within 5 years
Immunosuppressive therapy
Significant liver or kidney dysfunction
Treatment Regimen
Participants received oral Dasatinib (100mg) and Quercetin (500mg) daily for 12 weeks. This regimen was adapted from previous studies that demonstrated safety and senolytic activity in human tissues[@kirkland2020].
Endpoints
Primary Endpoints
Safety and tolerability of D+Q in AD patients
Change in cerebrospinal fluid (CSF) inflammatory markers
Reduction in peripheral senescence-associated biomarkers
Secondary Endpoints
Cognitive performance (ADAS-Cog, MMSE)
Brain imaging markers of neuroinflammation
Change in SASP factors in blood and CSF
Scientific Rationale
Preclinical Evidence
The translation of senolytic therapy to AD is supported by substantial preclinical evidence:
Mouse Models: Studies in AD mouse models showed that D+Q reduced senescent cell burden, decreased neuroinflammation, and improved cognitive function[@zhang2019].
Aging Brain Studies: Post-mortem studies of human brains revealed increased senescent cell burden in AD patients compared to age-matched controls[@baker2018].
Translational Studies: Pilot studies in humans demonstrated that D+Q reduces senescent cell markers in peripheral tissues[@justice2019].
Aging-Senescence Connection
This trial connects two major hallmarks of aging:
Cellular Senescence — the accumulation of terminally differentiated cells
[Neuroinflammation](/mechanisms/neuroinflammation) chronic activation of brain immune cells
The rationale posits that by addressing cellular senescence, we can interrupt one of the root causes of neuroinflammation in AD.
Results and Findings
Note: Specific trial results pending publication. The study completed enrollment and follow-up.
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[Baker DJ, et al., Clearance of p16-positive senescent cells by senolytics improves function in aged mice. Nature. 2016 (2016)](https://doi.org/10.1038/nature16943)
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[Justice JN, et al., Senolytics: bridging the gap between preclinical and clinical translation. Nat Rev Drug Discov. 2019 (2019)](https://doi.org/10.1038/s41573-019-0019-8)