Authors :
Zongshan Li, BS – Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing
Presenting Author: Yicong Lin, MD – Xuanwu Hospital, Capital Medical University, Beijing, China
Li Wang, MD – Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing
Shujuan Tian, MD – 河北医科大学第一医院
Chao Gao, MD – 河北医科大学第一医院
Xi Chen, MD – Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei
Dongxu Sun, MD – Suninflam Inc
Yuping Wang, MD, PhD – Xuanwu Hospital, Capital Medical University, Beijing, China
Rationale:
Drug-resistant epilepsy (DRE), affecting 30-40% of epilepsy patients, poses a significant therapeutic challenge. Emerging evidence implicates that Galectin-3 (Gal-3)-mediated neuroinflammation contributes to epileptogenesis, primarily via microglial activation and neuronal damage. Our preclinical studies demonstrated that SIF001, a novel anti-Gal-3 monoclonal antibody, significantly reduces proinflammatory cytokine release and microglial activation in vitro, while also decreasing seizure frequency and severity in murine models. This study aimed to evaluate the safety and preliminary efficacy of SIF001 in patients with DRE.
Methods:
This prospective, dual-center, open-label trial (ChiCTR2400089740) enrolled six patients with DRE who were ineligible for resective surgery from two epilepsy centers. Participants received intravenous SIF001 (50 mg/kg) on Days 1 and 15, with optional monthly maintenance doses for ≤1 year. The primary efficacy endpoint was the percentage reduction in seizure frequency at Day 28 compared to baseline, as recorded in seizure diaries. Secondary endpoints included changes in interictal epileptiform discharge frequency on EEG. Safety assessments were assessed by adverse events and laboratory tests.
Results:
Six patients (mean age 15.2 ± 7.2 years; 5 male), with diverse etiologies including Lennox-Gastaut Syndrome (unknown etiology), post-encephalitic and genetic-related epilepsy (mean duration 11.5 ± 7.8 years), completed the 28-day primary evaluation. At Day 28, the median seizure frequency reduction was 65.0% (IQR: 49.3-75.0%), with 66.7% (4/6) achieving ≥50% response and 16.7% (1/6) becoming seizure-free. EEG analysis (n=3) showed reduced epileptiform discharges in two patients. No serious adverse events or clinically significant laboratory abnormalities were observed.
Conclusions:
This first-in-human study provides preliminary clinical validation of Gal-3 targeting monoclonal antibody treatment in DRE, demonstrating SIF001's promising efficacy and favorable safety profile. These findings, congruent with robust preclinical anti-inflammatory and anti-seizure effects, support further investigation of SIF001 in larger, placebo-controlled trials to establish its long-term efficacy and safety as a novel, neuroinflammation-targeted therapy for refractory epilepsy.
Funding:
This work was supported by the National Key R&D Program of China (Grant No. 2022YFC2503800).