Developing antibodies against pathogenic TDP-43 in ALS

Johanne Kaplan, PhD, ProMIS™ Neurosciences, Inc., Cambridge, MA, introduces the TDP-43 program for amyotrophic lateral sclerosis (ALS) at ProMIS™ Neurosciences, Inc. Evidence suggests that the relocalization and accumulation of misfolded TDP-43 is key in ALS pathogenesis. The team has been looking to develop antibodies that are selective for pathogenic TDP-43 by identifying conformational epitopes only present on the misfolded form of the protein. The lead candidate, PMN267, shows selectivity for misfolded TDP-43 and initial pre-clinical data suggests it can block prion-like propagation and improve motor function in mice. There are currently two configurations of PMN267 in development: an intracellular intrabody to aid clearance of pathogenic aggregates inside cells and an extracellular antibody aimed at blocking propagation. This interview took place at the AD/PD™ 2023 congress in Gothenburg, Sweden.
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