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[1][2].
| 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 |
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[3].
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[4].
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[5].
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.
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:
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[6][7].
Inclusion Criteria:
Exclusion Criteria:
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[8].
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[9].
Aging Brain Studies: Post-mortem studies of human brains revealed increased senescent cell burden in AD patients compared to age-matched controls[10].
Translational Studies: Pilot studies in humans demonstrated that D+Q reduces senescent cell markers in peripheral tissues[11].
This trial connects two major hallmarks of aging:
The rationale posits that by addressing cellular senescence, we can interrupt one of the root causes of neuroinflammation in AD.
Note: Specific trial results pending publication. The study completed enrollment and follow-up.
Kirkland JL, Tchkonia T. Clinical strategies for targeting senolytics. Cell Metab. 2022. 2022. ↩︎
Passos JF, et al. Senolytics: a new therapeutic strategy for age-related diseases. Nat Rev Drug Discov. 2020. 2020. ↩︎
Baker DJ, et al. Clearance of p16-positive senescent cells by senolytics improves function in aged mice. Nature. 2016. 2016. ↩︎
He S, Sharpless NE. Senescence in health and disease. Cell. 2017. 2017. ↩︎
Zhu Y, et al. Identification of a novel senolytic agent that selectively eliminates senescent human fibroblasts. Aging Cell. 2015. 2015. ↩︎
Baker DJ, et al. Aging, cellular senescence, and Alzheimer's disease. Nat Rev Neurol. 2022. 2022. ↩︎
Ogrodnik M, et al. Cellular senescence drives age-dependent cognitive decline. Nature. 2019. 2019. ↩︎
Kirkland JL, et al. The clinical potential of senolytic drugs. J Am Geriatr Soc. 2020. 2020. ↩︎
Zhang P, et al. Senolytic therapy improves cognitive function in Alzheimer's disease mice. Nat Neurosci. 2019. 2019. ↩︎
Baker DJ, Petersen RC. Cellular senescence in brain aging and neurodegenerative diseases: evidence from p16INK4a. Acta Neuropathol. 2018. 2018. ↩︎
Justice JN, et al. Senolytics: bridging the gap between preclinical and clinical translation. Nat Rev Drug Discov. 2019. 2019. ↩︎