Anti-Aβ scFvs ameliorate Aβ-induced neurotoxicity in Drosophila

Date(s) - 02/21/2013
9:30 am

Krishanu Mathur, BME Masters Thesis Student

Alzheimer’s disease is a debilitating neurodegenerative disorder characterized by the presence of amyloid plaques and neurofibrillary tangles. With no known cure at present, investigations into different therapeutic strategies have produced varying results. Use of monoclonal antibodies targeted against amyloid beta (Aβ) has proven to be an efficient therapy strategy in animal models and has the potential to be translated into clinically relevant strategies. Replacing these antibodies with engineered antibodies, such as single chain variable fragments (scFvs), has allowed researchers to reap the efficacy of monoclonal antibodies while minimizing associated side-effects. For my thesis project, I investigate the effectiveness of two anti-Aβ scFvs, scFv-Ab9 and scFv-213, in arresting Aβ-induced neurodegeneration in a transgenic Drosophila disease model. We generated stable fly lines expressing two different anti-Aβ scFvs and effectively showed that these antibodies partially rescue flies from Aβ neurotoxicity. The rescue efficacy was additively enhanced by co-expression of both scFvs. This work highlights the application of Drosophila-based disease models in the efficient screening and validation of new therapeutic antibodies against Aβ neurotoxicity. These new, and more effective anti- Aβ antibodies can then be investigated further in rodent models and moved towards clinical trials.