Med (New York, N.Y.) · 2026
Mucoadhesive recombinant human catalase for dry eye disease: From protein engineering to first-in-human study.
СтатьяНазвание и аннотация: Перевод в очереди
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Shao Ming, Lu Yiteng, Xie Wenjie, Lu Annan, Jiang Yutong, Chen Xiaojing, Chai Yu, Le Qihua, Tian Lijia, Li Yongyun, Qiu Jini, Shan Kun, Wang Chenya, Hong Jiaxu, Liu Zhuang
Аннотация
BACKGROUND: Oxidative stress caused by excess reactive oxygen species (ROS) plays a key role in the progression of dry eye disease (DED), yet no approved DED therapy directly eliminates ROS. Here, we develop an antioxidant biologic with enhanced ocular-surface retention by thiol engineering of recombinant human catalase (hCAT) as a new ROS-scavenging eye drop therapy for DED.
METHODS: Thiolated hCAT (hCAT-SH) was characterized for activity, stability, mucin interaction, and ocular retention. Efficacy, mechanism, and safety were evaluated in mouse, rabbit, and rat studies, followed by a randomized, double-blind, placebo-controlled first-in-human trial in 30 patients with DED.
FINDINGS: With formulation optimization, hCAT-SH maintained enzymatic activity and formulation stability, while exhibiting enhanced mucin binding and prolonged corneal retention. In mouse DED models, hCAT-SH reduced oxidative stress, accelerated epithelial repair, restored tear secretion, and modulated inflammatory and barrier-repair pathways distinct from cyclosporine. In rabbits, exposure remained predominantly ocular with favorable repeated-dose tolerability. Clinically, 0.1 mg/mL hCAT-SH significantly improved corneal fluorescein staining, reduced tear cytokine levels and corneal dendritic cell density versus placebo, and raised no treatment-related safety concerns.
CONCLUSIONS: hCAT-SH is a carrier-free, long-retained H2O2-scavenging biologic, with integrated preclinical and first-in-human evidence supporting further development as a new DED drug.
FUNDING: National Natural Science Foundation of China; National Technology Innovation Center for Biopharmaceuticals; Jiangsu Key R&D Program; National Key R&D Program of China; Shanghai "Dawn" Program; Shanghai Science and Technology Innovation Action Plans; Shanghai Municipal Commission of Health; Shanghai High-Quality Development Plan for Science and Technology Industry; and Macao FDCT.
METHODS: Thiolated hCAT (hCAT-SH) was characterized for activity, stability, mucin interaction, and ocular retention. Efficacy, mechanism, and safety were evaluated in mouse, rabbit, and rat studies, followed by a randomized, double-blind, placebo-controlled first-in-human trial in 30 patients with DED.
FINDINGS: With formulation optimization, hCAT-SH maintained enzymatic activity and formulation stability, while exhibiting enhanced mucin binding and prolonged corneal retention. In mouse DED models, hCAT-SH reduced oxidative stress, accelerated epithelial repair, restored tear secretion, and modulated inflammatory and barrier-repair pathways distinct from cyclosporine. In rabbits, exposure remained predominantly ocular with favorable repeated-dose tolerability. Clinically, 0.1 mg/mL hCAT-SH significantly improved corneal fluorescein staining, reduced tear cytokine levels and corneal dendritic cell density versus placebo, and raised no treatment-related safety concerns.
CONCLUSIONS: hCAT-SH is a carrier-free, long-retained H2O2-scavenging biologic, with integrated preclinical and first-in-human evidence supporting further development as a new DED drug.
FUNDING: National Natural Science Foundation of China; National Technology Innovation Center for Biopharmaceuticals; Jiangsu Key R&D Program; National Key R&D Program of China; Shanghai "Dawn" Program; Shanghai Science and Technology Innovation Action Plans; Shanghai Municipal Commission of Health; Shanghai High-Quality Development Plan for Science and Technology Industry; and Macao FDCT.