HIRmAb-GDNF

**HIRmAb-GDNF** is a fusion protein drug engineered to deliver **glial cell line-derived neurotrophic factor (GDNF)** across the blood-brain barrier (BBB)[1][5]. It utilizes a monoclonal antibody (mAb) against the human insulin receptor (HIR) as a molecular "Trojan horse." The fusion protein is constructed by joining the amino terminus of GDNF to the carboxyl terminus of the CH3 region of the HIRMAb heavy chain. This bifunctional molecule binds both to the HIR on BBB endothelial cells (enabling transcytosis and CNS delivery) and to the GDNF receptor (GFRα1), mediating GDNF's neurotrophic activity[1][5].\nInitially developed as a potential therapy for **Parkinson's disease**, especially given the inability of native GDNF to cross the BBB, HIRmAb-GDNF was tested in primate models and showed increased CNS penetration compared to GDNF alone. However, primate studies revealed lack of neuroprotective efficacy and notable safety concerns (hypersensitivity, myocarditis, pancreatic lesions), suggesting risk for chronic use[1][5].

Brand names

HIRmAb-GDNF

Other names

HIRMAb-GDNF fusion protein