The DOI matches its Crossref record; 64 of the 65 references it cites were found in a registry or an index; none of the 99 sources its claims cite is checked for support yet.
Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial
Open accessAbstract
Preclinical studies indicate an age-associated accumulation of senescent cells across multiple organ systems. Emerging evidence suggests that tau protein accumulation, which closely correlates with cognitive decline in Alzheimer's disease and other tauopathies, drives cellular senescence in the brain. Pharmacologically clearing senescent cells in mouse models of tauopathy reduced brain pathogenesis. Compared to vehicle treated mice, intermittent senolytic administration reduced tau accumulation and neuroinflammation, preserved neuronal and synaptic density, restored aberrant cerebral blood flow, and reduced ventricular enlargement. Intermittent dosing of the senolytics, dasatinib plus quercetin, has shown an acceptable safety profile in clinical studies for other senescence-associated conditions. With these data, we proposed and herein describe the objectives and methods for a clinical vanguard study. This initial open-label clinical trial pilots an intermittent senolytic combination therapy of dasatinib plus quercetin in five older adults with early-stage Alzheimer's disease. The primary objective is to evaluate the central nervous system penetration of dasatinib and quercetin through analysis of cerebrospinal fluid collected at baseline and after 12 weeks of treatment. Further, through a series of secondary outcome measures to assess target engagement of the senolytic compounds and Alzheimer's disease-relevant cognitive, functional, and physical outcomes, we will collect preliminary data on safety, feasibility, and efficacy. The results of this study will be used to inform the development of a randomized, double-blind, placebo-controlled multicenter phase II trial to further explore of the safety, feasibility, and efficacy of senolytics for modulating the progression of Alzheimer's disease. Clinicaltrials.gov registration number and date: NCT04063124 (08/21/2019).
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In the paper
“aging is the single most robust risk factor of developing AD (6).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [6] Brookmeyer, 2019, Multistate models and lifetime risk estimation: application to Alzheimer's disease, Stat Med source
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In the paper
“Through dysregulation of p38 mitogen-activated protein kinases (p38MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), NOTCH, and mammalian target of rapamycin (mTOR) signaling, senescent cells can develop a senescence-associated secretory phenotype (SASP) (22, 23).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [22] Kritsilis, 2018, Ageing, cellular senescence and neurodegenerative disease, Int J Mol Sci source
- Not checked yetcites [23] Sharma, 2011, Possible underlying influence of p38MAPK and NF-κB in the diminished anti-anxiety effect of diazepam in stressed mice, J Pharmacol Sci source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The best characterized senolytic agents are dasatinib (D) plus quercetin (Q) (D+Q) (32).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [32] Gerdes, 2020, Cellular senescence in aging and age-related diseases: Implications for neurodegenerative diseases, Int Rev Neurobiol source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Overlapping expression of pathways implicated in senescence were common across tau-transgenic mice and human brain tissue with NFTs. These included tumor necrosis factor (TNF), interleukin 1β (IL-1β), and interferon gamma (IFN-γ), suggesting that these cells may accelerate neurodegeneration through release of toxic SASP factors.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [29] Musi, 2018, Tau protein aggregation is associated with cellular senescence in the brain, Aging Cell source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“NF-κB was the strongest upstream regulator of the NFT-associated gene expression profile.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [29] Musi, 2018, Tau protein aggregation is associated with cellular senescence in the brain, Aging Cell source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“In murine models, transplantation of senescent cells at a ratio of one to 10,000 with healthy cells was sufficient to engender frailty, physical disability, and premature mortality (18).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [18] Xu, 2018, Senolytics improve physical function and increase lifespan in old age, Nat Med source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Pathogenic tau propagates neuroinflammation through activation of microglia and astrocytes (33).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [33] Laurent, 2018, Tau and neuroinflammation: what impact for Alzheimer's disease and tauopathies?, Biomed J source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Transcriptomic analyses of neurons with or without NFTs in postmortem human brain tissue of individuals with AD revealed upregulation of genes associated with cellular senescence in NFT-bearing neurons. These included increased expression of genes related to cell survival and inflammation, as well as downregulation of genes implicated in apoptosis and cellular death.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [29] Musi, 2018, Tau protein aggregation is associated with cellular senescence in the brain, Aging Cell source
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In the paper
“Collectively, preclinical research has provided strong proof-of-concept data that tau-induced cellular senescence may be a novel therapeutic target for AD (29, 32).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Previous work by our team identified that cellular senescence in the brain is associated with tau-containing neurofibrillary tangles (NFTs), a hallmark feature of AD that closely correlates with cognitive decline (29).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [29] Musi, 2018, Tau protein aggregation is associated with cellular senescence in the brain, Aging Cell source
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- It may state two separate claims as one. 20
- Probably not a substantial claim. 9
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In the paper
“The SASP triggers immune cells to clear senescent cells, which is beneficial; however as senescent cells accumulate, the SASP exerts paracrine effects on adjacent cells, becoming the precipitant for broader cellular conversion to the senescent phenotype (17, 20).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
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In the paper
“Cellular senescence is a dynamic molecular process induced by stressors such as DNA and mitochondrial damage, telomere shortening, protein accumulation and metabolic dysfunction (17, 20).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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In the paper
“Cellular senescence is a hallmark feature of aging and contributes to numerous age-related chronic medical conditions including AD (10–19).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [10] Lewis-McDougall, 2019, Aged-senescent cells contribute to impaired heart regeneration, Aging Cell source
- Not checked yetcites [11] Nath, 2018, The murine dialysis fistula model exhibits a senescence phenotype: pathobiologic mechanisms and therapeutic potential, Am J Physiol Renal Physiol source
- Not checked yetcites [12] Ogrodnik, 2017, Cellular senescence drives age-dependent hepatic steatosis, Nat Commun source
- Not checked yetcites [13] Ogrodnik, 2019, Obesity-induced cellular senescence drives anxiety and impairs neurogenesis, Cell Metab source
- Not checked yetcites [14] Palmer, 2019, Targeting senescent cells alleviates obesity-induced metabolic dysfunction, Aging Cell source
- Not checked yetcites [15] Roos, 2016, Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice, Aging Cell source
- Not checked yetcites [16] Schafer, 2017, Cellular senescence mediates fibrotic pulmonary disease, Nat Commun source
- Not checked yetcites [17] Tchkonia, 2018, Aging, cell senescence, and chronic disease: emerging therapeutic strategies, JAMA source
- Not checked yetcites [18] Xu, 2018, Senolytics improve physical function and increase lifespan in old age, Nat Med source
- Not checked yetcites [19] Zhu, 2015, The Achilles' heel of senescent cells: from transcriptome to senolytic drugs, Aging Cell source
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In the paper
“The SASP consists of a noxious secretome comprised of pro-inflammatory cytokines, proteases, chemokines, and extracellular matrix degrading proteins (24–27).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [24] Acosta, 2013, A complex secretory program orchestrated by the inflammasome controls paracrine senescence, Nat Cell Biol source
- Not checked yetcites [25] Chen, 2015, MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-associated secretory phenotype, Mol Cell source
- Not checked yetcites [26] Hoare, 2016, NOTCH1 mediates a switch between two distinct secretomes during senescence, Nat Cell Biol source
- Not checked yetcites [27] Weichhart, 2018, mTOR as regulator of lifespan, aging, and cellular senescence: a mini-review, Gerontology source
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In the paper
“The strong association between aging and AD suggests overlapping molecular and cellular processes (9), which may serve as viable treatment targets to prevent or alleviate neurodegenerative diseases.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [9] Xia, 2018, Aging and Alzheimer's disease: comparison and associations from molecular to system level, Aging Cell source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The burden of senescent cells in the brain increases with advanced chronological age and neurodegenerative diseases, and occurs across cell types including neurons, microglia, astrocytes, oligodendrocyte precursor cells, and endothelial cells (28–32).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [28] Baker, 2018, Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives, J Clin Invest source
- Not checked yetcites [29] Musi, 2018, Tau protein aggregation is associated with cellular senescence in the brain, Aging Cell source
- Not checked yetcites [30] Zhang, 2019, Senolytic therapy alleviates Abeta-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model, Nat Neurosci source
- Not checked yetcites [31] Blasko, 2004, How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes, Aging Cell source
- Not checked yetcites [32] Gerdes, 2020, Cellular senescence in aging and age-related diseases: Implications for neurodegenerative diseases, Int Rev Neurobiol source
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None of the sources cited for this claim have been checked yet.
In the paper
“Microglia and astrocytes can acquire a senescent phenotype themselves (28, 31, 32), promoting further diffusion of the SASP and the conversion of healthy cells to the senescent phenotype.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [28] Baker, 2018, Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives, J Clin Invest source
- Not checked yetcites [31] Blasko, 2004, How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes, Aging Cell source
- Not checked yetcites [32] Gerdes, 2020, Cellular senescence in aging and age-related diseases: Implications for neurodegenerative diseases, Int Rev Neurobiol source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“To date, research conducted across six transgenic AD mouse models has demonstrated that orally administered senolytic drugs ablate senescent cells in the brain and alleviate AD-relevant pathogenesis (28–30, 32).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [28] Baker, 2018, Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives, J Clin Invest source
- Not checked yetcites [29] Musi, 2018, Tau protein aggregation is associated with cellular senescence in the brain, Aging Cell source
- Not checked yetcites [30] Zhang, 2019, Senolytic therapy alleviates Abeta-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model, Nat Neurosci source
- Not checked yetcites [32] Gerdes, 2020, Cellular senescence in aging and age-related diseases: Implications for neurodegenerative diseases, Int Rev Neurobiol source
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In the paper
“D+Q target multiple senescent cell types; the combination of the two agents has been demonstrated to effectively clear senescent cells and alleviate numerous chronic medical conditions in preclinical models, including physical frailty, muscle weakness, vascular stiffness, osteoporosis, and hepatic stenosis (12–15, 18, 34).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [12] Ogrodnik, 2017, Cellular senescence drives age-dependent hepatic steatosis, Nat Commun source
- Not checked yetcites [13] Ogrodnik, 2019, Obesity-induced cellular senescence drives anxiety and impairs neurogenesis, Cell Metab source
- Not checked yetcites [14] Palmer, 2019, Targeting senescent cells alleviates obesity-induced metabolic dysfunction, Aging Cell source
- Not checked yetcites [15] Roos, 2016, Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice, Aging Cell source
- Not checked yetcites [18] Xu, 2018, Senolytics improve physical function and increase lifespan in old age, Nat Med source
- Not checked yetcites [34] Hickson, 2019, Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease, EBioMedicine source
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None of the sources cited for this claim have been checked yet.
In the paper
“Importantly, D+Q have been well tolerated and demonstrated benefits in first-in-human clinical trials of other conditions (i.e., idiopathic pulmonary fibrosis (40) followed by diabetic kidney disease (34).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [40] Justice, 2019, Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study, EBioMedicine source
- Not checked yetcites [34] Hickson, 2019, Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease, EBioMedicine source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“Both D and Q have demonstrated blood-brain barrier penetrance in rodent models with some supportive data in clinical studies of individuals undergoing cancer treatment (41, 42).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [41] Porkka, 2008, Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia, Blood source
- Not checked yetcites [42] Ishisaka, 2011, Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats, Free Radic Biol Med source
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In the paper
“Brain MRI indicated that senolytic treatment mitigated pathogenic ventricular enlargement, aberrant blood flow, and the SASP.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [29] Musi, 2018, Tau protein aggregation is associated with cellular senescence in the brain, Aging Cell source
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In the paper
“Our pilot study evaluating a novel therapeutic agent for AD is a direct follow-up to the preclinical studies and clinical trials utilizing D+Q for other age-related conditions, which demonstrated an encouraging safety profile coupled with modest but promising therapeutic outcomes (18, 34, 40–42).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Discussion
What the sources say
- Not checked yetcites [18] Xu, 2018, Senolytics improve physical function and increase lifespan in old age, Nat Med source
- Not checked yetcites [34] Hickson, 2019, Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease, EBioMedicine source
- Not checked yetcites [40] Justice, 2019, Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study, EBioMedicine source
- Not checked yetcites [41] Porkka, 2008, Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia, Blood source
- Not checked yetcites [42] Ishisaka, 2011, Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats, Free Radic Biol Med source
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In the paper
“Similarly, in an open-label trial of D+Q for diabetic kidney disease, short-term treatment effectively reduced senescent cell burden in adipose tissue and attenuated plasma levels of key SASP factors, including IL-2 and IL-6 (34).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [34] Hickson, 2019, Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease, EBioMedicine source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The first clinical trial of senolytic treatment, published in 2019, showed D+Q was generally well tolerated and suggested improvements in physical function in an open-label trial for individuals with idiopathic pulmonary fibrosis, a fatal disease, providing encouraging first evidence for further clinical testing (40).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Introduction
What the sources say
- Not checked yetcites [40] Justice, 2019, Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study, EBioMedicine source
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In the paper
“We will track occurrence of adverse events (AEs) and serious adverse events (SAEs) from the screening visit to the end of the study.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Methods > Secondary Outcome Measures
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In the paper
“AEs and SAEs will be defined according to the International Conference on Harmonization Guidance for Clinical Safety Data Management.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Methods > Secondary Outcome Measures
What the sources say
- Not checked yetcites International Conference on Harmonization Guidance for Clinical Safety Data Management
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In the paper
“While it has been shown that D and/or Q can cross the blood barrier in rodent models and individuals undergoing cancer treatment, the central nervous system drug penetrance in individuals with AD remains unknown (41, 42).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Discussion
What the sources say
- Not checked yetcites [41] Porkka, 2008, Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia, Blood source
- Not checked yetcites [42] Ishisaka, 2011, Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats, Free Radic Biol Med source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Incidence of AEs and SAEs will be reviewed by the UTHSCSA Data Safety Monitoring Board (DSMB).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Methods > Secondary Outcome Measures
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In the paper
“This initial open-label clinical trial pilots an intermittent senolytic combination therapy of dasatinib plus quercetin in five older adults with early-stage Alzheimer’s disease.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Abstract
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In the paper
“One of the major challenges to our trial and related studies as this field moves forward is the lack of a universally accepted definition and biomarkers of cellular senescence (57).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Discussion
What the sources say
- Not checked yetcites [57] DiBattista, 2020, NIA workshop on senescence in brain aging and Alzheimer's disease and its related dementias, GeroScience source
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In the paper
“Preclinical and clinical trials have identified various cellular and molecular features of cellular senescence (58).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Discussion
What the sources say
- Not checked yetcites [58] Tuttle, 2020, Cellular senescence and chronological age in various human tissues: a systematic review and meta-analysis, Aging Cell source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“The intermittent administration of senolytics in other study populations has been shown to attenuate side effects and effectively circumvent potential off-target effects induced by continuous receptor occupancy.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Discussion
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Senolytic treated mice had lower tau deposition, which correlated with favorable clinically relevant outcomes.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Discussion
What the sources say
- Not checked yetcites [29] Musi, 2018, Tau protein aggregation is associated with cellular senescence in the brain, Aging Cell source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As such, the SToMP-AD vanguard is critical in that it will provide the first proof-of-concept AD-relevant data utilizing a senescence-associated pharmacotherapy.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Discussion
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- Rests on an assumption: Cellular senescence has not been examined in clinical trials of aMCI or early-stage AD.
In the paper
“CSF tau levels demonstrate elevation prior to tau PET imaging, suggesting that it may be a sensitive marker of early change (59).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Discussion
What the sources say
- Not checked yetcites [59] Mattsson, 2017, (18)F-AV-1451 and CSF T-tau and P-tau as biomarkers in Alzheimer's disease, EMBO Mol Med source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The senescence markers included in the secondary aim were selected a priori based on the literature.”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Though there are obvious benefits to being able to repurpose a FDA approved chemotherapeutic medication, D, with a well-established side effect profile (53), there is a need to carefully evaluate safety and the equipoise of treatment in our vulnerable target population, especially as D+Q are utilized in combination to achieve broader targeting of senescent cell survival mechanisms (19).”
§ Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial > Discussion
What the sources say
- Not checked yetcites [53] Sprycel prescribing information, 2018
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Cerebrospinal fluid concentrations of dasatinib and quercetin reflect central nervous system penetration of these drugs.
“The primary objective is to evaluate the central nervous system penetration of dasatinib and quercetin through analysis of cerebrospinal fluid collected at baseline and after 12 weeks of treatment.”
The paper relies on this without support.
The central nervous system drug penetrance of D+Q in individuals with AD is unknown.
“While it has been shown that D and/or Q can cross the blood barrier in rodent models and individuals undergoing cancer treatment, the central nervous system drug penetrance in individuals with AD remains unknown (41, 42).”
The paper relies on this without support.
Cellular senescence has not been examined in clinical trials of aMCI or early-stage AD.
“However, as no clinical trials of aMCI and early-stage AD have examined cellular senescence, it is possible that the treatment regimen will affect various cellular and molecular senescence markers, which will be determined though exploratory analyses of a broader panel of senescence markers.”
The paper relies on this without support.
D+Q is the most well-established senolytic.
“Though there are several senolytic compounds which have been identified and are being further studied (e.g., fisetin and other flavonoids) for their associations with improvements in cognition and reductions in AD-relevant pathology (36, 49–52), D+Q was selected for use in this first AD relevant trial as it is the most well established.”
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In the citing paper
“As previously described29, the open-label, proof-of-concept, Phase I, single-site pilot study protocol included the completion of 11 study visits over a period of 20–24 weeks (Fig. 1).”
From Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial (2023) · cites this paper as [29]
Experimental — accuracy not yet measuredIn the citing paper
“The application of senolytics for patients diagnosed with early-stage AD has recently been investigated, yielding preliminary findings that suggest a potential role for these agents in managing neurodegenerative diseases.79,80”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [79]
In the citing paper
“The ability of senolytic therapy to modulate the progression of AD is also being evaluated in a pilot clinical trial. 32”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [32]
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The stated drug-free interval does not fit the two-week cycle
MinorTwo dosing days followed by 14 no-drug days make a 16-day cycle. That conflicts with the stated two-week cycle and visits scheduled 14 days apart, affecting the treatment schedule.
“Eligible participants will be administered 100 mg of D (one 100 mg capsule, Sprycel, Bristol Myers Squibb) and 1000 mg of Q (four 250 mg capsules, Thorne Research) daily for two consecutive days followed by a 14-day (+/− 2 day) no-drug period to complete a single cycle.”
“On the first day of each 2-week drug cycle, participants will present to the study site for safety assessments and drug dispensing (weeks 1, 3, 5, 7, 9, 11).”
Citations
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“Moreover, disease-modifying effects were observed with a partial (35%) decrease in NFTs, which was consistent with preclinical studies of senolytic treatment for other models of aging and disease (10-16, 18, 19, 30, 54-56).”
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“Moreover, disease-modifying effects were observed with a partial (35%) decrease in NFTs, which was consistent with preclinical studies of senolytic treatment for other models of aging and disease (10-16, 18, 19, 30, 54-56).”
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BackgroundMethodInfluentialSelf-citation
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“14,27,28 To date, four human studies administering DQ as a combination senolytic therapy have been completed in various populations, including idiopathic pulmonary fi brosis, 29 diabetic kidney disease, 30 age-related osteoporosis, 31 and Alzheimer ’ s disease.”
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Senotherapeutics for Brain Aging Management
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A Review on Phyto-Therapeutic Approaches in Alzheimer’s Disease
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Senolytic Treatment Improve Small Intestine Regeneration in Aging
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Metadata
- Authors
- Gonzales, M. M., Garbarino, V. R., Marques Zilli, E., Petersen, R. C., Kirkland, J. L., Tchkonia, T., Musi, N., Seshadri, S., Craft, S., & Orr, M. E.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Mayo Clinic (US)
- Boston University (US)
- Wake Forest University Health Sciences (US)
- Corresponding author
- Gonzales, Mitzi M.
- Orr, Miranda E.
- ORCID
- Venue
- The Journal of Prevention of Alzheimer's Disease
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 9
- Issue
- 1
- Pages
- 22-29
- ISSN
- 2274-5807 (ISSN-L)
- PMC
- PMC8612719
- OpenAlex
- W3216516063
- Cited by
- 203
- References
- 65
- Citations by year
- 2026: 34 · 2025: 52 · 2024: 55 · 2023: 41 · 2022: 18
- FWCI
- 18.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- The Journal of Prevention of Alzheimer s Disease (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK2BX003804)
- National Institute on Aging (R33AG061456, P30AG013319, U24AG059624, R01AG068293, P30AG044271)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- senolytic therapy, Alzheimer's disease, dasatinib, quercetin, cellular senescence, tau accumulation, tauopathy, intermittent dosing, cerebrospinal fluid drug penetration, neuroinflammation, cognitive decline, early Alzheimer's disease, older adults
- MeSH terms
- Dasatinib, Senotherapeutics, Aged, Alzheimer Disease, Animals, Humans, Cellular Senescence, Tauopathies, Mice
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