Monoclonal full-length antibody against TAR DNA binding protein 43 reduces related proteinopathy in neurons

• DOI: 10.1172/jci.insight.140420
• Publication Date: 2020-10-06T16:01:18Z
• Authors: Silvia Pozzi; Philippe Codron; Geneviève Soucy; Laurence Renaud; Pierre Junior Cor...; Kallol Dutta; Christine Bareil; Jean-Pierre Julien
• Keywords: Frontotemporal lobar degeneration

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), 2 incurable neurodegenerative disorders, share the same pathological hallmark named TDP43 (TAR DNA binding protein 43) proteinopathy. This event is characterized by a consistent cytoplasmic mislocalization aggregation of TDP43, which loses its physiological properties, leading neurons to death. Antibody-based approaches are now emerging interventions in field disorders. Here, we tested target specificity, vivo distribution, therapeutic efficacy monoclonal full-length antibody, E6, TDP43-related conditions. We observed that antibody recognizes specifically fraction TDP43. demonstrated ability targeting large spinal cord mice reducing NF-κB activation. also recognized proteasome as well lysosome machineries possible mechanisms used reduce To our knowledge, this first report showing feasibility against proteinopathy an ALS/FTLD mouse model.