Senolytics for Alzheimer's Disease

Overseen By Ronald Petersen, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Pregnancy, Uncontrolled diabetes, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 11 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, Dasatinib and Quercetin (a type of senolytic therapy), to determine their safety and feasibility for individuals with mild cognitive impairment (MCI) or Alzheimer's disease. The researchers aim to explore whether these treatments can help improve or manage symptoms of these conditions. Participants will take the treatments orally for two days every two weeks over approximately three months. Ideal candidates for the trial are those diagnosed with Alzheimer's or MCI who do not plan to travel extensively during the study period. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications listed in Appendix 1 during the days the investigational product is administered and for 36 hours after. If you are on cholinesterase inhibitors or memantine, you must be on a stable dose for at least three months.

Is there any evidence suggesting that Dasatinib and Quercetin are likely to be safe for humans?

Research has shown that using Dasatinib and Quercetin together appears safe for people. Studies have found that older adults, including those with mild memory issues or at risk for Alzheimer's, can take these drugs without major problems.

In one study, participants reported no serious side effects, suggesting the treatment is generally safe for older adults. Another study also found that participants handled the treatment well without major issues.

These findings offer reassurance about the safety of taking Dasatinib and Quercetin together. However, staying informed and consulting a healthcare professional about any concerns before joining a clinical trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about dasatinib and quercetin for Alzheimer's disease because they target senescent cells, which are aging cells that can negatively affect brain health. Unlike standard treatments for Alzheimer's, which often focus on managing symptoms and neurotransmitter levels, this combination aims to tackle one of the underlying causes of the disease. By clearing these harmful cells, dasatinib and quercetin could potentially slow down or even reverse the progression of Alzheimer's, offering a novel approach that could change the way we understand and treat this condition.

What evidence suggests that Dasatinib and Quercetin might be an effective treatment for Alzheimer's disease?

Research has shown that combining dasatinib and quercetin might boost brain functions. In studies with older rats, this treatment improved learning and memory. Other studies in mice found enhancements in both physical and mental abilities with this combination. Early human trials suggested that these drugs could enhance blood flow in the brain and improve thinking skills in older adults. In this trial, participants with MCI or Alzheimer's disease will receive the combination of dasatinib and quercetin. Researchers are studying this treatment because it targets old cells that no longer divide and release harmful substances, which are believed to contribute to Alzheimer's disease. ^{1 2 3 6 7}

Who Is on the Research Team?

Vijay K. Ramanan, MD, PhD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for men and women aged 55 or older with Mild Cognitive Impairment or Alzheimer's, confirmed by brain imaging showing Tau protein. They must not be on certain dementia medications or if they are, the dose should be stable for three months. Participants need a legal representative to consent and attend visits, have no major travel plans for about three months, and meet specific health criteria like adequate blood counts.

Inclusion Criteria

Availability and consent from a LAR

Participants must have no plans to travel over the ~3 months between Visits 3 and 14 that interfere with study visits

You have been diagnosed with symptomatic probable Alzheimer's disease and have a certain range of scores on memory and mental tests.

Exclusion Criteria

Unwilling or unable to give informed consent

Pregnancy

Your lab test results are not normal, or a doctor thinks there may be a problem based on your overall health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dasatinib and Quercetin for 2 days out of every 15 days for 6 cycles

11 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dasatinib and Quercetin

Trial Overview The ALSENLITE study tests the combination of two drugs, Dasatinib and Quercetin, to see if they're safe and can work in people with Mild Cognitive Impairment (MCI) or Alzheimer's disease. The goal is to understand how these drugs affect cognitive impairment associated with Alzheimer's.

How Is the Trial Designed?

Group I: Dasatinib plus Quercetin Treatment Goup Experimental Treatment 2 Interventions

Subjects with MCI or Alzheimer's disease will take Dasatinib and Quercetin by mouth at the same times for 2 days out of every 15 days for 6 cycles lasting for a total of 77 days (12 concurrent doses of each agent).

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

James L. Kirkland, MD, PhD

Lead Sponsor

Trials

2

Recruited

80+

Published Research Related to This Trial

In a 12-week pilot study involving 5 participants with early-stage Alzheimer's disease, the combination of dasatinib and quercetin was well-tolerated, showing safety and feasibility without significant adverse effects or early discontinuations.

The treatment successfully penetrated the central nervous system, with dasatinib detected in cerebrospinal fluid, suggesting potential for targeting cellular senescence in Alzheimer's, although cognitive improvements were not observed in this small trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Senolytic therapy to modulate the progression of Alzheimer's Disease (SToMP-AD) - Outcomes from the first clinical trial of senolytic therapy for Alzheimer's disease. Gonzales, MM., Garbarino, VR., Kautz, T., et al.[2023]

In a study using SAMP10 mice, which model brain aging, the combination of dasatinib and quercetin significantly improved frailty, motor, and cognitive functions compared to a control group, indicating potential benefits of senolytic therapy in aging.

SAMP10 mice exhibited greater frailty characteristics than normal aging controls (SAMR1), and the combination therapy not only reduced these frailty markers but also positively affected the senescent phenotype in the hippocampus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice. Ota, H., Kodama, A.[2022]

The phase I clinical trial involving 5 early-stage Alzheimer's patients demonstrated that the senolytic therapy dasatinib and quercetin was well-tolerated, with no early discontinuations and confirmed CNS penetrance of dasatinib in cerebrospinal fluid.

While the treatment did not show significant cognitive improvements, it provided safety data and insights into potential senolytic effects, indicating a need for further studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial. Gonzales, MM., Garbarino, VR., Kautz, TF., et al.[2023]

Both senolytic treatments, ABT-263 and dasatinib + quercetin (D+Q), effectively preserved cognitive function and maintained the integrity of the blood-brain barrier in aging male rats, suggesting their potential as therapies to combat cognitive decline.

D+Q was found to influence a greater number of genes related to inflammation and synaptic function compared to ABT-263, indicating that while both treatments are beneficial, D+Q may have a broader impact on brain health and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of peripheral cellular senescence on brain aging and cognitive decline. Budamagunta, V., Kumar, A., Rani, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8833137/

Combination of dasatinib and quercetin improves cognitive ... Aged rats following D+Q treatment displayed improved learning abilities and effective acquisition of spatial short- and long-term memory of a new place compared ...

2. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00056-8/fulltext

A pilot study of senolytics to improve cognition and mobility ... Studies have demonstrated that co-administration of Dasatinib and Quercetin improved aspects of both physical and cognitive function in mice.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05422885?intr=Dasatinib%20%2B%20Quercetin&rank=2

Safety and Feasibility of Dasatinib and Quercetin in Adults ... The study will evaluate whether giving D+Q may improve cerebral blood flow regulation, mobility, and cognition in older adults, and thus may prevent progression ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724003571

Senolytic Therapy to Modulate the Progression of ... Intermittent dosing of the senolytics, dasatinib plus quercetin, has shown an acceptable safety profile in clinical studies for other senescence-associated ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10875739/

Senolytic therapy in mild Alzheimer's disease - PubMed Central 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 ...

6. marcusinstituteforaging.org marcusinstituteforaging.org/news/pilot-study-suggests-treatment-may-improve-cognition-older-adults-risk-alzheimers-disease

Pilot Study Suggests Treatment May Improve Cognition in ... “Our findings suggest that senolytic treatment with dasatinib and quercetin is well-tolerated in older adults at risk for Alzheimer's disease ...

7. newsroom.wakehealth.edu newsroom.wakehealth.edu/news-releases/2023/09/clinical-trial-shows-treatment-designed-to-clear-senescent-cells-in-alzheimers-disease-is-safe

Phase I Clinical Trial Shows Treatment Designed to Clear ... Quercetin was not detected in the CSF of any participants. “We also determined that the treatment was safe, feasible and well-tolerated,” Orr ...