Chimeric proteins comprising an N-terminal domain derived from an N-terminal nucleotide binding domain of TDP-43 and a C-terminal domain derived from a splicing repressor are described. These proteins may be administered to a subject to treat or prevent disease manifesting TDP-43 proteinopathy such as inclusion body myocytosis, amyotrophic lateral sclerosis (ALS), or frontotemporal dementia (FTD).
