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cTfRMAb-EPO is a **chimeric fusion protein** created by fusing erythropoietin (EPO) to a chimeric monoclonal antibody against the transferrin receptor (TfR), specifically designed to enable **transport of EPO across the blood-brain barrier (BBB)** via **TfR-mediated transcytosis**[7][3][5]. The antibody is specific for mouse TfR and binds with high affinity (KD ~2.6 nM), while the EPO domain retains neuroprotective activity by binding to mouse erythropoietin receptor (EPOR, ED50 ~0.33 nM)[3][7]. This bifunctional molecule acts as a “molecular Trojan horse,” facilitating brain delivery of EPO, which otherwise does not penetrate the BBB effectively[3][9][7]. It was engineered and expressed in Chinese hamster ovary cells, and has been studied extensively in mouse models of Alzheimer’s disease (AD), tauopathy, and Parkinson’s disease for its neuroprotective properties, such as reducing brain amyloid-beta (Aβ) load, phosphorylated tau, neuroinflammation, and synaptic loss, and improving behavioral and cognitive outcomes[1][2][5][9]. The fusion protein shows a rapid peripheral clearance due to TfR-mediated removal from the circulation, with a 10–14 fold faster clearance rate compared to native EPO, resulting in reduced hematologic side effects at neurotherapeutic doses[2][7][3]. Preclinical studies indicate improved hematological safety and neuroprotection compared to recombinant human EPO, supporting further development for neurodegenerative disorders[2][1][4].
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