Development of a humanized anti-fibrin monoclonal antibody for the treatment of neuroinflammatory and retinal diseases.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro and animal research without human subjects
PubMed 41408289 · doi:10.1186/s12974-025-03650-w
What was done
Researchers engineered THN391, a humanized, affinity-matured monoclonal antibody lacking Fc effector function, designed to specifically neutralize the cryptic inflammatory fibrin epitope γ377–395. Structural and binding properties were characterized to verify selectivity over fibrinogen and lack of anticoagulant interference. Efficacy was tested in preclinical rodent models: experimental autoimmune encephalomyelitis (EAE) in mice (for multiple sclerosis) and laser-induced neovascular lesions in rats (for neovascular age-related macular degeneration).
What was found
THN391 demonstrated 100-fold greater affinity than the murine 5B8 antibody, blocked fibrin binding to CD11b/c complement receptors, and spared fibrinogen and normal coagulation. Both THN391 and its Fc-intact version reduced demyelination, inflammatory foci, and clinical scores in EAE mice. In the rat neovascularization model, THN391 reduced lesion size to an extent comparable to standard-of-care VEGF antagonists. The abstract reports no exact numerical values, sample sizes, or confidence intervals.
Why it matters
Targeting the inflammatory fibrin epitope without affecting baseline coagulation provides a potential therapeutic candidate for neurodegenerative and retinal vascular diseases without bleeding liability.
Limits
Evidence is restricted to in vitro assays and animal disease models. The abstract omits sample sizes (n), quantitative effect sizes, dosing parameters, pharmacokinetic data, and statistical certainty measures.
Cited by
- supports Researcher Katerina Akassoglou developed a therapeutic antibody that blocks the interaction between fibrinogen and microglia to prevent neuroinflammation.