IL-2 for Alzheimer's Disease

Overseen By Alireza Faridar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Methodist Hospital Research Institute

Must be taking: Stable AD meds

Must not be taking: Antipsychotics, Antiepileptics, Corticosteroids, others

Disqualifiers: Infections, Cardiac dysfunction, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment for Alzheimer's disease that aims to reduce brain inflammation. The study tests a drug called Interleukin-2 (IL-2), which may help manage immune system activity and slow disease progression. Participants will receive IL-2 or a placebo through injections to assess its effects on inflammation and overall safety. The trial seeks participants with mild to moderate Alzheimer's who have been on stable medication for at least a month. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications, but you need to be on a stable dose of any medications affecting cognition for at least 4 weeks before the trial and remain stable during the study. Some medications, like certain antipsychotics and antiepileptics, are restricted, so check with the trial team about your specific medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that low-dose interleukin-2 (IL-2) is generally safe for individuals with mild to moderate conditions like Alzheimer's disease. In one study, all participants completed the trial without serious side effects. The IL-2 treatment increased the number of regulatory T cells, which help maintain immune system balance. Another study confirmed that low-dose IL-2 is safe and well-tolerated, showing positive results in reducing signs of inflammation. These findings suggest that IL-2 could be a promising and safe option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard Alzheimer's treatments, which often focus on managing symptoms or slowing disease progression, Aldesleukin (a form of Interleukin-2) offers a unique approach by potentially modulating the immune system. Researchers are excited about Aldesleukin because it might enhance the body's natural ability to clear harmful proteins linked to Alzheimer's disease progression. This immune system modulation is a novel mechanism compared to current options, like cholinesterase inhibitors and NMDA receptor antagonists, which primarily focus on neurotransmitter activity. The potential for Aldesleukin to offer a new pathway for treatment is what makes it stand out in the field.

What evidence suggests that IL-2 might be an effective treatment for Alzheimer's?

Research shows that low-dose interleukin-2 (IL-2) holds promise for treating Alzheimer's disease. Studies have found that it can safely increase certain cells in the body that help control inflammation. In Alzheimer's patients, this treatment reduced harmful inflammation and improved memory and thinking skills. These findings suggest that IL-2 may slow the disease by balancing the immune system. Overall, evidence supports IL-2 as a potential treatment for Alzheimer's disease. Participants in this trial will receive either Aldesleukin every 2 weeks, Aldesleukin every 4 weeks, or a placebo to further evaluate its effectiveness. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals aged 50-86 with mild to moderate Alzheimer's Disease (AD), as indicated by MMSE scores of 12-26. Participants must have a diagnosis according to NIA-AA criteria, speak English, and have at least eight years of education. They should be stable on current medications for other conditions and meet specific health requirements related to liver function, blood counts, and kidney function.

Inclusion Criteria

English language speaking

Formal education of eight or more years

Your albumin level is 3.0mg/dL or higher.

Exclusion Criteria

I do not have any serious infections or tuberculosis.

You have certain heart or blood pressure issues, uncontrolled diabetes, recent cancer history, hepatitis, certain disabilities, or are taking specific medications or drugs that may make you unsuitable for the study.

I do not have severe heart problems like recent heart attacks or uncontrolled heart rhythm issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive five-day-courses of subcutaneous IL-2 or placebo for a total of 6 months

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Interleukin-2

Trial Overview The study tests low dose Interleukin-2 (IL-2) against a placebo in AD patients. It's a phase II trial where participants are randomly assigned to receive either IL-2 or placebo via subcutaneous injections over six months. The aim is to assess the safety of IL-2 therapy and its effects on inflammation in both the brain and body.

How Is the Trial Designed?

Group I: Aldesleukin every 4 weeks Active Control 1 Intervention

Group II: Aldesleukin every 2 weeks Active Control 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Interleukin-2 is already approved in United States, European Union for the following indications:

Approved in United States as Aldesleukin for:

• Metastatic melanoma
• Metastatic renal cell carcinoma

Approved in European Union as PROLEUKIN for:

• Metastatic renal cell carcinoma

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Published Research Related to This Trial

Interleukin-1 (IL-1) is overexpressed in the brains of Alzheimer's patients, contributing to plaque formation and neuronal changes that are characteristic of the disease.

Genetic studies indicate that specific polymorphisms in the IL-1A and IL-1B genes significantly increase the risk of developing Alzheimer's disease, particularly at an earlier age, highlighting the role of IL-1 in the disease's pathogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-1, neuroinflammation, and Alzheimer's disease. Mrak, RE., Griffin, WS.[2022]

The IL-1A allele 2 is identified as a significant genetic risk factor for Alzheimer's disease (AD), with a dose-dependent effect; having two copies of this allele increases the risk of developing AD by approximately three times compared to having none.

This association holds true across different age groups, indicating that the IL-1A allele 2 contributes to AD risk in both early-onset and late-onset cases, based on a study of 298 AD patients and 306 control subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene dose-dependent association of interleukin-1A [-889] allele 2 polymorphism with Alzheimer's disease. Combarros, O., Sánchez-Guerra, M., Infante, J., et al.[2006]

The TNF-α-308 G/A gene polymorphism is significantly associated with an increased risk of late-onset Alzheimer's disease (LOAD), suggesting it may influence the brain's inflammatory response in affected individuals.

In contrast, the TNF-α-863 C/A polymorphism does not show a significant association with LOAD, indicating that not all TNF-α gene variations impact the disease risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic association of TNF-α-308 G/A and -863 C/A polymorphisms with late onset Alzheimer's disease in Azeri Turk population of Iran. Ardebili, SM., Yeghaneh, T., Gharesouran, J., et al.[2021]

In a study involving 42 patients with cerebral amyloid angiopathy-related hemorrhage (CAAH), 232 Alzheimer's disease (AD) patients, and 167 non-AD controls, the IL-1A allele 2 was not found to be associated with an increased risk of CAAH.

The results suggest that the IL-1A allele 2 or 2,2 genotype does not significantly contribute to the risk of CAAH, indicating that other factors, such as apolipoprotein E alleles, may play a more critical role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between interleukin-1A polymorphism and cerebral amyloid angiopathy-related hemorrhage. McCarron, MO., Stewart, J., McCarron, P., et al.[2016]

Interleukin 2 can cause a wide range of side effects, including systemic symptoms like fever and chills, as well as serious complications such as capillary leak syndrome and renal dysfunction, with a mortality rate of 1 to 3%.

The severity of these side effects is dose-dependent and can be influenced by the administration regimen and other cytokine combinations, highlighting the need for careful patient selection and specialized care during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse effects of interleukin 2]. Ravaud, A., Negrier, S., Lakdja, F., et al.[2009]

Recombinant interleukin-2 is an effective immunomodulating agent that has shown promising results in treating renal cell carcinoma and melanoma, particularly in patients who do not respond well to conventional therapies.

While it can lead to significant adverse effects like hypotension and renal dysfunction, these effects are generally reversible, and its administration requires careful monitoring in a critical-care setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant interleukin-2: a biological response modifier. Kintzel, PE., Calis, KA.[2007]

Chronic treatment with high doses of recombinant interleukin-2 in old mice led to significant impairments in memory functions and notable neuronal cell loss specifically in the hippocampus, indicating potential neurotoxic effects in older populations.

In contrast, adult mice treated with interleukin-2 did not show any differences in memory performance or neuron density compared to controls, suggesting that the negative effects of this treatment may be age-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of chronic treatment with recombinant interleukin-2 on the central nervous system of adult and old mice. Nemni, R., Iannaccone, S., Quattrini, A., et al.[2019]

In a study of 7 patients, interleukin-2 (IL2) administration led to cognitive impairments, as evidenced by neuropsychological tests and changes in event-related potentials (P300).

The observed effects included increased latency and decreased amplitude of P300, indicating disrupted cerebral function, but these changes were reversible after IL2 treatment was stopped.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological and neurophysiological assessment of the central effects of interleukin-2 administration. Caraceni, A., Martini, C., Belli, F., et al.[2019]

In a review of eight patients undergoing IL2-based immunotherapy, new neurological issues such as confusion, seizures, and coma developed, linked to brain lesions primarily in the occipital and cerebellar regions.

After stopping IL2 treatment, seven out of eight patients showed significant recovery in neurological function and resolution of brain lesions, suggesting that the neurological effects were likely related to the IL2 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple cerebral lesions complicating therapy with interleukin-2. Karp, BI., Yang, JC., Khorsand, M., et al.[2019]

In APP/PS1 mice, a significant imbalance between regulatory T (Treg) cells and IL-17-producing helper T (Th17) cells was observed during the progression of Alzheimer's disease, particularly at the middle disease stage.

Low-dose recombinant human IL-2 treatment effectively restored the balance of Treg and Th17 cells, reduced neuroinflammation, decreased Aβ plaque deposition, and slowed cognitive decline, suggesting its potential as a novel immunotherapy for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose IL-2 Treatment Rescues Cognitive Deficits by Repairing the Imbalance Between Treg and Th17 Cells at the Middle Alzheimer's Disease Stage. Yuan, L., Xie, L., Zhang, H., et al.[2023]

In patients with Alzheimer's disease (AD), increased interleukin-2 (IL-2) production correlates with the severity of the disease, particularly in those with moderately-severe AD and vascular dementia (VaD).

Both mild and moderately-severe AD patients showed significantly higher interleukin-6 (IL-6) levels compared to VaD patients and controls, suggesting that IL-6 may be involved in the pathogenesis of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-2 and IL-6 secretion in dementia: correlation with type and severity of disease. Huberman, M., Sredni, B., Stern, L., et al.[2019]

Patients with Alzheimer's disease showed similar levels of interleukin-1 and -2 production in their peripheral blood mononuclear cells compared to age-matched controls, suggesting that these immune responses may not be significantly altered in Alzheimer's.

In contrast, healthy young individuals produced significantly higher levels of interleukin-1 than both Alzheimer's patients and age-matched controls, indicating a potential difference in immune function related to age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lymphokine production in patients with Alzheimer's disease. Bessler, H., Sirota, P., Hart, J., et al.[2019]

The study involving 51 Alzheimer's disease patients and 36 control subjects found no significant association between the IL-6-174G/C polymorphism and the incidence of Alzheimer's disease, suggesting that this genetic variant may not be a risk factor for developing the condition.

However, there was a notable observation that the IL-6 G/G and IL-6-174G/C genotypes were more frequently found in women with Alzheimer's, indicating potential sex-based differences in genetic risk factors that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polymorphism 174 G/C of interleukin 6 gene in Alzheimer's disease--preliminary report. Paradowski, B., Celczyńska, D., Dobosz, T., et al.[2015]

Interleukin-1 (IL-1) is elevated in Alzheimer's disease and promotes the expression of the beta-amyloid precursor protein (APP), suggesting a link between inflammation and amyloid production in the disease.

The study proposes that certain APP proteins may have protease inhibitor activity that could activate IL-1 and Nerve Growth Factor (NGF), indicating potential feedback loops that affect neuronal survival and function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focusing on IL-1-promotion of beta-amyloid precursor protein synthesis as an early event in Alzheimer's disease. Blume, AJ., Vitek, MP.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40615880/

Low-dose interleukin-2 in patients with mild to moderate ... In this study, we evaluated the safety and efficacy of two dosing frequencies of low-dose Interleukin-2 (IL-2) in expanding Tregs to modify disease progression ...

2. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-025-01791-x

Low-dose interleukin-2 in patients with mild to moderate ... In this study, we evaluated the safety and efficacy of two dosing frequencies of low-dose Interleukin-2 (IL-2) in expanding Tregs to modify disease progression ...

3. ir.coyatherapeutics.com ir.coyatherapeutics.com/news/news-details/2024/Coya-Therapeutics-Announces-Positive-Results-of-a-Double-Blind-Study-of-Subcutaneous-Low-Dose-Interleukin-2-LD-IL-2-in-Alzheimers-Disease-AD-Presented-at-the-Clinical-Trials-on-Alzheimers-Disease-Conference-CTAD24-in-Madrid-Spain/default.aspx

News Details The study successfully met its primary and secondary endpoints, demonstrating that treatment with low-dose interleukin-2 is safe and well- ...

4. neurologylive.com neurologylive.com/view/low-dose-interleukin-2-reduces-proinflammatory-biomarkers-phase-2-study-alzheimers

Low-Dose Interleukin-2 Reduces Proinflammatory ... Low-dose interleukin-2 (COYA 301) reduced proinflammatory biomarkers and improved cognitive scores in early-stage Alzheimer's disease patients.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0140673625002624

Efficacy and safety of low-dose IL-2 as an add-on therapy ... The primary endpoint was survival at 640 days (21 months). Secondary outcomes included safety, ALS Functional Rating Scale-Revised (ALSFRS-R) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12231701/

Low-dose interleukin-2 in patients with mild to moderate ... In this study, we evaluated the safety and efficacy of two dosing frequencies of low-dose Interleukin-2 (IL-2) in expanding Tregs to modify disease progression ...