Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Neurology

Amyotrophic lateral sclerosis (ALS)

Eukaryotic translation initiation factor 2a kinase 3 (EIF2AK3; PERK); TAR DNA binding protein 43 (TDP-43; TARDBP)

Studies in flies and primary rat neurons suggest inhibiting EIF2AK3 could help treat ALS. In a
tdp-43-expressing fly model of ALS, siRNA-mediated or pharmacological inhibition of PERK decreased deficits in climbing ability and increased eif2a phosphorylation compared with no inhibition. In rat primary cortical neurons expressing Tdp-43, a PERK inhibitor decreased Tdp-43-associated toxicity compared with vehicle. Next steps include using the ALS fly model to identify other cellular pathways that play a role in EIF2A phosphorylation and TDP-43
toxicity.

SciBX 7(3); doi:10.1038/scibx.2014.94
Published online Jan. 23, 2014

Patented; licensed by FoldRx Pharmaceuticals Inc., which Pfizer Inc. acquired in 2010

Kim, H.-J. et al. Nat. Genet.;
published online Dec. 15, 2013;
doi:10.1038/ng.2853
Contact: Nancy M. Bonini, University of Pennsylvania, Philadelphia, Pa.
e-mail:
nbonini@sas.upenn.edu