Senolytic Therapy to Modulate Progression of Alzheimer's Disease

Summary

The purpose of this pilot study is to evaluate whether a combination of two drugs, dasatinib (D) and quercetin (Q) \[D+Q\], penetrate the brain using cerebrospinal fluid (CSF) in older adults with early Alzheimer's disease (AD). This combination of drug therapy has been shown to affect dying cells in humans with other chronic illnesses and in Alzheimer's mice models. The study team want to know if this combination of medications will reach the brain in order to evaluate if this intervention may be effective for treating AD symptoms in future studies. This is also known as a "proof of concept" study.

Timeline

Start

2020-02-14

Primary completion

2021-12-10

Completion

2023-01-30

Publications

• Garbarino VR, Palavicini JP, Melendez J, Barthelemy NR, He Y, Kautz TF, Lopez-Cruzan M, Mathews JJ, Xu P, Zhang B, Saliba A, Ragi N, Sharma K, Mason D, Johnson S, Hendrix S, Craft S, Petersen RC, Espindola-Netto JM, Xue A, Tchkonia T, Kirkland JL, Salardini A, Musi N, Bateman RJ, Gonzales MM, Orr ME. Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer's disease. Neurotherapeutics. 2025 Jul;22(4):e00591. doi: 10.1016/j.neurot.2025.e00591. Epub 2025 Apr 23.
• Andrews TD, Day GS, Irani SR, Kanekiyo T, Hickson LJ. Uremic Toxins, CKD, and Cognitive Dysfunction. J Am Soc Nephrol. 2025 Jun 1;36(6):1208-1226. doi: 10.1681/ASN.0000000675. Epub 2025 Feb 26.
• Garbarino VR, Palavicini JP, Melendez J, Barthelemy N, He Y, Kautz TF, Lopez-Cruzan M, Mathews JJ, Xu P, Zhan B, Saliba A, Ragi N, Sharma K, Craft S, Petersen RC, Espindola-Netto JM, Xue A, Tchkonia T, Kirkland JL, Seshadri S, Salardini A, Musi N, Bateman RJ, Gonzales MM, Orr ME. Evaluation of Exploratory Fluid Biomarker Results from a Phase 1 Senolytic Trial in Mild Alzheimer's Disease. Res Sq [Preprint]. 2024 Mar 8:rs.3.rs-3994894. doi: 10.21203/rs.3.rs-3994894/v1.
• Gonzales MM, Garbarino VR, Kautz TF, Palavicini JP, Lopez-Cruzan M, Dehkordi SK, Mathews JJ, Zare H, Xu P, Zhang B, Franklin C, Habes M, Craft S, Petersen RC, Tchkonia T, Kirkland JL, Salardini A, Seshadri S, Musi N, Orr ME. Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial. Nat Med. 2023 Oct;29(10):2481-2488. doi: 10.1038/s41591-023-02543-w. Epub 2023 Sep 7.
• Sarkar P, Kumar A, Behera PS, Thirumurugan K. Phytotherapeutic targeting of the mitochondria in neurodegenerative disorders. Adv Protein Chem Struct Biol. 2023;136:415-455. doi: 10.1016/bs.apcsb.2023.02.013. Epub 2023 Mar 24.
• Gonzales MM, Garbarino VR, Marques Zilli E, Petersen RC, Kirkland JL, Tchkonia T, Musi N, Seshadri S, Craft S, Orr ME. Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial. J Prev Alzheimers Dis. 2022;9(1):22-29. doi: 10.14283/jpad.2021.62.
• Gonzales MM, Krishnamurthy S, Garbarino V, Daeihagh AS, Gillispie GJ, Deep G, Craft S, Orr ME. A geroscience motivated approach to treat Alzheimer's disease: Senolytics move to clinical trials. Mech Ageing Dev. 2021 Dec;200:111589. doi: 10.1016/j.mad.2021.111589. Epub 2021 Oct 21.

Drugs

Indications