AAV-Ep + IgG1-GA

AAV-Ep + IgG1-GA is an experimental gene therapy designed for the treatment of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) associated with the C9orf72 G4C2 repeat expansion. The therapy utilizes a novel AAV-Ep+ capsid, which is optimized for efficient transduction of neurons and ependymal cells in the brain. This vector delivers the genetic sequence for a high-affinity IgG1 monoclonal antibody (IgG1-GA) that specifically targets toxic glycine-alanine (GA) repeat-associated non-AUG (RAN) proteins. The mechanism of action involves a dual clearance pathway: intracellularly, the antibody-GA complexes are targeted for proteasomal degradation via interaction with the E3 ubiquitin ligase TRIM21; extracellularly, the secreted antibodies bind GA-RAN proteins and facilitate their uptake and degradation through Fc receptor-mediated pathways. Preclinical studies in C9-BAC mouse models have demonstrated that this approach reduces RAN protein load, mitigates neuroinflammation, improves motor behavior, and increases survival.

Other names

AAV-Ep+ anti-GA RAN protein antibody therapyAAV-Ep+IgG1-GA immunotherapy