From cryptic exons to neuronal dysfunction: combinatorial antisense makes sense in TAR DNA-binding protein-43 (TDP-43) pathology

Signal Transduction and Targeted Therapy, vol. 11

Abstract

In a recent study published in Science Translational Medicine , Guo et al. 1 shed further light on TDP-43 pathology by demonstrating that several transcripts involved in synaptic function and membrane excitability are aberrantly spliced upon depletion of TDP-43. Simultaneous treatment with antisense oligonucleotides targeting these transcripts corrected the splicing abnormalities and restored neuronal function, suggesting that combination therapy could be a promising approach in TDP-43 proteinopathies. 1

Authors 2

1. Gianluca Figlia Aachen Institute of Neuropathology

   Universitätsklinikum Aachen

   Affiliation as printed

   Institute of Neuropathology, Uniklinik RWTH Aachen, Aachen, Germany

2. Juliane Bremer corresponding Aachen Institute of Neuropathology

   Universitätsklinikum Aachen

   Affiliation as printed

   Institute of Neuropathology, Uniklinik RWTH Aachen, Aachen, Germany. jbremer@ukaachen.de