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Low-Dose IL-2 Shows Potential for Alzheimer Disease, Phase 2a Trial Underway
After promising findings in a small, open-label, phase 1 pilot study of low-dose interleukine-2 (IL-2) immunotherapy in patients with Alzheimer disease (AD), researchers are proceeding with a double-blinded, randomized, placebo-controlled, phase 2a trial, according to a letter published in Translational Neurodegeneration.
The phase 1 study, as described in the letter, evaluated the safety and feasibility of low-dose IL-2 administration to expand regulatory T cells (Tregs) in 8 patients with AD.
“Preclinical studies have suggested variable effects of Treg modification on the neurodegenerative process,” wrote corresponding author Stanley H. Appel, MD, of the Houston Methodist Research Institute, Houston, Texas, and study coauthors. “While some studies propose that the Treg population might obstruct a selective gateway for immune cell trafficking to the central nervous system, thereby compromising reparative immune responses, an increasing number of preclinical studies, including ours, indicate that systemic Treg expansion through IL-2 administration or ex vivo expanded Treg administration effectively modulates neuroinflammation and alleviates AD pathology.”
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To investigate the effect of Treg expansion in humans with AD, participants in the open-label study received a daily fixed dose of subcutaneous recombinant human IL-2 injection for 5 consecutive days. The 5-day treatment cycle was repeated 3 times over a total 4 months. After the last treatment cycle, participants completed a 2-month follow-up phase.
All 8 patients completed treatment and follow-up, according to the letter, and no serious adverse events were reported after IL-2 administration. The most common adverse events were injection site irritation/redness (37.5%) and mild leukopenia (37.5%).
Blood samples showed that low-dose IL-2 expanded the Treg population, suppressed peripheral pro-inflammatory monocytes, and reduced plasma myeloid activating chemokines in participants, researchers reported. Clinical assessments revealed improvements on the Mini-Mental State Examination and a trend toward improvement on the Clinical Dementia Rating Scale Sum of Boxes. Nevertheless, the study’s small sample size, short duration of treatment, and lack of a placebo group limited interpretation of those results.
A phase 2a trial is currently underway to confirm and expand the findings, the researchers announced.
“In this proof-of-concept trial, the impact of IL-2 immunotherapy on established AD biomarkers, cognitive, and functional endpoints are being assessed,” they wrote. “Additionally, we will investigate whether the IL-2-induced peripheral Treg expansion will modify neuroinflammation in AD individuals.”
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