Assessing toxicity and allergenicity of therapeutic monoclonal antibodies for neurodegenerative diseases

Abstract

Numerous anti-PrP and anti-Aβ monoclonal antibodies have been developed for the treatment of prion diseases and AD, respectively. Previously, proteins linked with 'apoptosis' were identified in vivo and in vitro after cross-linking PrPC with motif specific anti-PrP antibodies. It is worth noting that prior reports of antibody-mediated "neurotoxic" effects were based on microscopic assessments, but not on molecular analysis. To gain a better understanding of the proteome changes that occur in neuroblastoma cell lines, anti-PrPC antibodies were applied directly to neuronal cells or cells were co-cultured with antibody-treated microglia. In this thesis, I hypothesised that in addition to the neuronal apoptosis induced by anti-PrP antibodies, cross-linking PrPC with anti-PrP antibodies might also induce a neuronal allergenic response.

Date of Thesis submission	2021
Original language	English
Awarding Institution	Western Sydney University
Supervisor	Mourad Tayebi (Supervisor) & Tim Karl (Supervisor)