Home › Research › Biomarkers
Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial
Gonzales MM, Garbarino VR, Kautz TF, Palavicini JP, Lopez-Cruzan M, Dehkordi SK, Mathews JJ, Zare H et al.. Nature medicine, 2023-09-07
Topic: Drug trials: efficacy and safety
Cellular senescence contributes to Alzheimer's disease (AD) pathogenesis. An open-label, proof-of-concept, phase I clinical trial of orally delivered senolytic therapy, dasatinib (D) and quercetin (Q), was conducted in early-stage symptomatic patients with AD to assess central nervous system (CNS) penetrance, safety, feasibility and efficacy. Five participants (mean age = 76 + 5 years; 40% female) completed the 12-week pilot study. D and Q levels in blood increased in all participants (12.7-73.5 ng ml -1 for D and 3.29-26.3 ng ml -1 for Q). In cerebrospinal fluid (CSF), D levels were detected in four participants (80%) ranging from 0.281 to 0.536 ml -1 with a CSF to plasma ratio of 0.422-0.919%; Q was not detected. The treatment was well-tolerated, with no early discontinuation. Secondary cognitive and neuroimaging endpoints did not significantly differ from baseline to post-treatment further supporting a favorable safety profile. CSF levels of interleukin-6 (IL-6) and glial fibrillary acidic protein (GFAP) increased (t(4) = 3.913, P = 0.008 and t(4) = 3.354, P = 0.028, respectively) with trending decreases in senescence-related cytokines and chemokines, and a trend toward higher Aβ42 levels (t(4) = -2.338, P = 0.079). In summary, CNS penetrance of D was observed with outcomes supporting safety, tolerability and feasibility in patients with AD. Biomarker data provided mechanistic insights of senolytic effects that need to be confirmed in fully powered, placebo-controlled studies. ClinicalTrials.gov identifier: NCT04063124 .
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Gonzales, M. M., Garbarino, V. R., Kautz, T. F., Palavicini, J. P., Lopez-Cruzan, M., Dehkordi, S. K., et al. (2023). Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial. Nature medicine. https://doi.org/10.1038/s41591-023-02543-w
Vancouver
Gonzales MM, Garbarino VR, Kautz TF, Palavicini JP, Lopez-Cruzan M, Dehkordi SK, et al. Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial. Nature medicine. 2023. doi:10.1038/s41591-023-02543-w. PMID: 37679434.
BibTeX
@article{gonzales2023-37679434,
author = {Gonzales, M. M. and Garbarino, V. R. and Kautz, T. F. and Palavicini, J. P. and Lopez-Cruzan, M. and Dehkordi, S. K. and Mathews, J. J. and Zare, H. and others},
title = {{Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial}},
journal = {Nature medicine},
year = {2023},
doi = {10.1038/s41591-023-02543-w},
pmid = {37679434},
url = {https://doi.org/10.1038/s41591-023-02543-w}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Secondary cognitive and neuroimaging endpoints did not significantly differ from baseline to post-treatment further supporting a favorable safety profile.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designopen-label trial
- Effect size0.919%
- Evidence strengthLow
How this study scored 55/100
Published in a top-tier journal. Scored zero for study design and sample size because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 32 of the 58 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | Design recorded as “open-label trial”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 1 / 2 | Blinded or placebo-controlled (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37679434) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 32 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 32 of the 58 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Biomarkers
Also tagged “monoclonal”
332 studies in the library carry the topic tag “monoclonal”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 332 tagged studies.