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Join us as PhD in Applied Life Sciences student Joshua Yang speaks about the development of a brain penetrating erythropoietin for Alzheimer’s disease.
“Alzheimer’s disease is a chronic neurodegenerative disease with no cure. Recent studies have shown that Erythropoietin (EPO), a hematopoietic growth factor, has neurotrophic effects in the brain. However, the blood-brain barrier (BBB) reduces EPO’s accessibility to the brain. Transferrin receptor monoclonal antibodies (TfRMAbs) can act as molecular Trojan horses and shuttle the therapeutic into the brain across the BBB. TfRMAbs have Fc effector function side-effects which result in suppression of reticulocytes. Previous work shows that removal of the Fc N-linked glycosylation site can reduce the impact of the Fc-mediated effector function. The effect of these Fc mutations on the pharmacokinetics of plasma- and brain-concentration, and clearance of TfRMAb-based fusion proteins has not been studied. Additionally, lower doses of the TfRMAb-based fusion proteins may lower the potential for such side-effects. In this project, we hypothesize that reducing the dose of the wild-type TfRMAb-EPO or utilizing the mutant TfRMAb-N292G-EPO will reduce the Fc effector function side-effects associated with cTfRMAbs.”
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