PhD Student, Joshua Yang: PhD Dissertation Defense Presentation – “The Development of a Brain Penetrating Erythropoietin for the Treatment of Alzheimer’s Disease”

Please join us for PhD Student, Joshua Yang’s PhD Dissertation Defense Presentation on “The Development of a Brain Penetrating Erythropoietin for the Treatment of Alzheimer’s Disease”

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by amyloid plaques, neurofibrillary tangles, and microgliosis. Erythropoietin (EPO), a neurotrophin, is a potential therapeutic for AD but has limited blood-brain barrier (BBB) permeability. A fusion protein of EPO and the transferrin receptor monoclonal antibody (cTfRMAb-EPO) acts as a molecular Trojan horse by shuttling EPO into the brain via the transvascular route. The cTfRMAb-EPO fusion protein has displayed neuroprotective effects in the APP/PS1 mouse model of amyloidosis. However, cTfRMAbs have Fc-effector function adverse effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly (cTfRMAb-N292G-EPO) reduces these side-effects. This dissertation seeks to explore the pharmacokinetics of this mutant fusion protein and investigate the neuroprotective effects in the PS19 mouse model of tauopathy. Additionally, this research aims to develop a novel method of measuring brain concentration of a neurotherapeutic utilizing Amicon Ultra Centrifugal filters for tissue sample preparation. The raw brain homogenate contains many proteins and macromolecules, interfering with the limit of detection of assays. This method enhances the signal compared to using raw brain homogenate samples thus improving the currently used immunoassays used to detect IgG-based fusion proteins in brain tissue homogenates.

Date: January 3, 2022

Time:  12:00 – 1:00 p.m.

Location: 535 Bldg. – 152 Classroom (Zoom link will be sent out with Outlook invite)