Despite major research efforts, treatments that slow or halt the progression of Alzheimer’s disease (AD) remain limited. Evidence increasingly suggests that inflammation in the brain and body contributes to the initiation and progression of the disease. To better understand this connection, scientists are exploring how inflammatory signaling pathways influence neurodegenerative processes.

Dr. Alireza Faridar, a neurologist at Houston Methodist, evaluates these pathways and their potential as therapeutic targets. Developing new therapeutic approaches for AD is one of his primary interests. Recently, Dr. Faridar received the Part the Cloud (PTC) award from the Alzheimer’s Association, which includes an investment of approximately $1 million. This translational research funding will support a Phase 1/Phase 2a double-blind clinical trial to evaluate a combination therapy of IL-2 (interleukin-2) and the GLP-1 (glucagon-like peptide-1) receptor agonist semaglutide to target neuroinflammation in AD.

Part the Cloud awards fund high-risk, high-reward translational research for Alzheimer's disease and related dementias

Founded by Michaela “Mikey” Hoag, PTC is a global research program within the Alzheimer’s Association that funds early-stage clinical trials to slow, stop or cure AD and other dementias. PTC grants are designed to accelerate the translation of experimental treatments from the laboratory into clinical trials – a phase often referred to as “the valley of death”. To date, PTC has awarded more than $90 million in research grants, with $1.6 billion in follow-on funding, and funded 83 clinical studies of novel potential treatments. PTC has achieved more than 1700% return on its investments since its inception in 2012 and aims to maintain this ROI.

In a press release, the Alzheimer’s Association said that PTC stands out as the only funding mechanism of its kind, with its effectiveness shown by over $1.6 billion in subsequent funding from the federal government, venture capital firms and other sources.

In 2026, the PTC awarded more than$11 million to advance transformational AD and dementia therapeutics. Of this amount, approximately $1 million was awarded to Dr. Faridar to support a clinical trial evaluating the combinatorial therapeutic approach of IL-2 and semaglutide.

“If successful, this study will provide the first evidence that a dual immunotherapeutic strategy can safely modify disease-related processes in AD. Such findings would lay the foundation for larger clinical trials and could open the door to a new, multimodal approach to slowing or preventing Alzheimer’s progression.”

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Alireza Faridar, MD

Why this clinical trial is targeting regulatory T cells

A sub-population of immune cells called regulatory T cells (Treg cells) are master regulators of inflammation in the blood and brain. Treg cells are vital for maintaining immune tolerance and suppressing inflammation. However, loss of Treg cell function shifts the immune system toward a pro-inflammatory status.

Patients suffering from AD experience both quantitative and functional impairment of Treg cells. The suppressive capacity of Treg cells is often compromised in AD patients, leading to unchecked inflammation (in both blood and brain) and accelerated cognitive decline.

“Regulatory T-cell immunophenotype and function are compromised in Alzheimer's disease. Following ex vivo expansion, the immunomodulatory function of regulatory T cells is enhanced even at advanced stages of Alzheimer's disease,” says Dr. Faridar.

Risk factors for Alzheimer’s disease

Obesity and type 2 diabetes are two modifiable risk factors for AD and other dementias. Specifically, hypercholesterolemia, hypertension, atherosclerosis and diabetes mellitus are common comorbidities associated with AD. Therefore, one of the most effective strategies to alter AD’s trajectory and delay the onset of cognitive decline is to mitigate these risk factors.

Half of dementia cases are thought to be preventable by targeting 14 modifiable risk factors. These include obesity, diabetes, hypertension, smoking, depression, physical inactivity, excessive alcohol use, traumatic brain injury, poor education, air pollution, social isolation and high LDL cholesterol.

Combinatorial treatment strategy to advance Alzheimer’s therapeutics

Dr. Faridar discovered that pairing low-dose IL-2 with semaglutide has synergistic effects. Dr. Faridar proposes that IL-2 may reduce brain inflammation, slow the progression and accumulation of tau protein in the brain, and thereby prevent the progression of AD.

Treg cells are a potentially restorable therapeutic target in AD. To restore and expand Treg cells in AD patients, Dr. Faridar developed a treatment strategy that combines IL-2 (a drug that can restore Treg cell function) with semaglutide (also called Ozempic, which is FDA-approved for diabetes and weight loss).

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that mimics the hormone GLP-1, which is released in the gut after eating. GLP-1 slows stomach emptying, signals a feeling of fullness to the brain, and stimulates insulin secretion from the pancreas. Furthermore, semaglutide has additional effects that improve energy metabolism and energy balance.

Relationship between semaglutide and Alzheimer’s disease

Large-scale clinical trials have established that semaglutide does not treat AD. However, semaglutide has been associated with a lower risk of AD-related dementias among patients with type 2 diabetes. Studies suggest that semaglutide may indirectly support brain health by mitigating risk factors such as obesity, cardiovascular disease and neuroinflammation.

The phase 1/phase 2a clinical trial to evaluate the co-administration of IL-2 and semaglutide

The 3-year clinical trial includes three arms:

• Placebo

• Low dose IL-2 monotherapy

• Combination of IL-2 and semaglutide

The study will enroll 24 individuals (eight per arm) with mild-to-moderate AD aged 50 to 86. Inclusion criteria include a confirmed AD diagnosis based on amyloid PET brain imaging and a mini-mental state examination score between 16 and 26.

The effects on inflammatory markers, Alzheimer’s pathology biomarkers (β-amyloid and tau) and cognitive function will be evaluated in this study.

The study's findings could prompt larger clinical trials to assess this combined treatment approach as a possible therapy to slow down AD progression.

AD is heterogeneous and has a complex pathology. Modern neuroscience conceptualizes AD as a network of interacting biological processes rather than a linear cascade of events. The exact mechanism by which AD and other dementias are caused remains unclear. The strategy of combining IL-2 and semaglutide may address the complex pathobiology of AD from multiple angles. This study may also aid researchers in mapping interacting networks across genetic, metabolic and neuroimmune levels to develop effective AD therapeutics.

For further information on Dr. Faridar’s research on this topic, please see the following references: