Troculeucel Linked to Plasma GFAP Changes and Cognitive Measures in Early Alzheimer Disease Studies

Early-phase data suggest that plasma glial fibrillary acidic protein (GFAP) may serve as a biomarker of treatment response in patients with Alzheimer disease (AD) receiving troculeucel (SNK01; NKGen Biotech), an investigational natural killer (NK) cell therapy designed to modulate neuroinflammation. Overall, newly presented findings from 2 phase 1 studies demonstrated correlations between plasma GFAP levels and cognitive scores, supporting the potential role of the biomarker in monitoring therapeutic effects in early-stage clinical trials.¹

The data, presented at the 2026 AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases, held March 17-21 in Copenhagen, Denmark, evaluated plasma GFAP as a biomarker for anti-inflammatory response and cognitive outcomes in patients treated with troculeucel across 2 phase 1 studies. For context, plasma GFAP, a marker of astrocytic activation and neuroinflammation, has increasingly been explored as a blood-based biomarker in neurodegenerative disease research.²

In the phase 1 dose-escalation study (NCT04678453), 10 patients received intravenous troculeucel every 3 weeks for 3 months, with a total of 4 infusions administered at doses of 1 billion, 2 billion, or 4 billion cells. In the other phase 1 study (NCT06189963), 3 patients with moderate AD received 6 billion cells every 3 weeks over a 12-month period. Investigators assessed plasma GFAP concentrations and cognitive outcomes using the Alzheimer Disease Composite Score (ADCOMS) and the Clinical Dementia Rating–Sum of Boxes (CDR-SB) at baseline and 3 months following treatment.¹

At baseline, plasma GFAP levels showed statistically significant positive correlations with cognitive impairment measures, including CDR-SB (r = 0.60; P = .045) and ADCOMS (r = 0.64; P = .030). After 3 months of treatment with troculeucel, similar associations were observed between GFAP levels and cognitive outcomes, with correlations reported for CDR-SB (r = 0.57; P = .056) and ADCOMS (r = 0.66; P = .022).¹

Investigators noted that the consistency in correlation strength and direction across baseline and post-treatment assessments suggested that plasma GFAP levels remain closely associated with cognitive status in this patient population. Overall, these findings may indicate that GFAP could serve as a responsive biomarker for tracking anti-inflammatory effects of NK-cell–based therapies in early-stage clinical research.

Read more: FDA Fast Tracks Innovative Cell Therapy Troculeucel for Alzheimer Disease

Troculeucel, developed by NKGen Biotech, is an autologous, non–genetically modified NK-cell therapy engineered through proprietary expansion methods to enhance cytotoxicity and increase expression of activating receptors. The therapy is designed to augment the body’s innate immune response and potentially reduce neuroinflammatory processes implicated in neurodegenerative disorders. Investigators have hypothesized that enhanced NK-cell activity may help clear pathological proteins and attenuate inflammatory signaling pathways associated with disease progression.¹

Although the studies were limited by small sample sizes and exploratory analyses, the authors reported that the data provide preliminary support for further investigation of troculeucel in neurodegenerative disease. They also highlighted the potential utility of plasma GFAP as a blood-based biomarker for evaluating treatment response and disease activity in future trials.

According to the investigators, larger studies will be needed to confirm whether changes in plasma GFAP reflect therapeutic modulation of neuroinflammation and whether these biomarker changes translate into clinically meaningful cognitive outcomes in patients with AD.¹

REFERENCES
1. Song P, Hong S, Kang Y, et al. PLASMA GFAP AS A BIOMARKER FOR ANTI-INFLAMMATORY RESPONSE AND COGNITIVE IMPROVEMENT IN PHASE 1 TRIALS OF TROCULEUCEL FOR ALZHEIMER’S DISEASE. Presented at: AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases; March 17-21, 2026; Copenhagen, Denmark.
2. Benedet AL, Milà-Alomà M, Vrillon A, et al. Plasma GFAP as a biomarker of astrocytic activation in Alzheimer disease. Nat Med. 2021;27(12):2159-2166. doi:10.1038/s41591-021-01569-9.