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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of Dasatinib, a cancer drug, and Quercetin, a plant compound, to help people over 55 with memory problems or Alzheimer's disease. The goal is to see if these drugs can safely remove damaged cells in the brain. By doing so, it might slow down or improve the symptoms of Alzheimer's disease. Dasatinib plus quercetin has been previously tested in an early-stage Alzheimer's disease study.

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.

What data supports the effectiveness of the drug combination of dasatinib and quercetin for Alzheimer's disease?

Research shows that dasatinib and quercetin can clear senescent cells, which are linked to Alzheimer's disease, in animal models. In a small human trial, the drug combination was well-tolerated and showed potential for reducing markers associated with Alzheimer's, although more studies are needed to confirm its effectiveness. ^{1 2 3 4 5}

Is senolytic therapy with dasatinib and quercetin safe for humans?

In early clinical trials for Alzheimer's disease, the combination of dasatinib and quercetin was generally well-tolerated with no early discontinuations and only mild to moderate side effects reported. Previous studies in other conditions also suggest an acceptable safety profile for these senolytics. ^{1 2 3 5 6}

How is the drug dasatinib and quercetin unique for Alzheimer's disease?

Dasatinib and quercetin are unique for Alzheimer's disease because they target and clear senescent cells (old cells that have stopped dividing) in the brain, which may help reduce harmful protein buildup and inflammation linked to the disease. This approach is different from other treatments that typically focus on symptoms rather than the underlying cellular aging process. ^{1 2 3 5 7}

Research Team

Vijay K. Ramanan, MD, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial. [2023]

3. United States 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. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Translating the Biology of Aging into New Therapeutics for Alzheimer's Disease: Senolytics. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Combination of dasatinib and quercetin improves cognitive abilities in aged male Wistar rats, alleviates inflammation and changes hippocampal synaptic plasticity and histone H3 methylation profile. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Effect of peripheral cellular senescence on brain aging and cognitive decline. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice. [2022]