Perampanel selective non-competitive AMPA receptor antagonist:  \cite{Aizawa2019}

Downreguation of adenosine deaminase acting on RNA 2 (ADAR2) occurs in sporadic ALS (sALS) \cite{Kawahara_2004} . ADAR2 is an RNA adenosine-to-inosine  (A-to-I) mRNA editing enzyme. Modifying mRNA adenosine to inosine (translated into guanosine), results in new protein isoforms, and it is a dynamic process which diversifies the proteome \cite{Rosenthal2012}. The influx of Ca2+ through  α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors  is regulated by ADAR2 A-to-I editing. However, in sALS, ADAR2 is deficient and the majority of patients with sALS have a GluA2 subunit of the glutamate AMPA receptor that is unedited \cite{Kawahara_2004}. The outcome of this loss of glutamate AMPA editing is that Ca2+ permeability is elevated, and this is associated with TDP-43 pathology. Perampanel is a non-competitive, selective antagonist of the AMPA receptor. In mice in which the AMPA receptor is knocked out in motor neurons to model sALS, perampanel greatly attenuates neuopathology, decreased motor neuron death and prevented the TDP-43 mislocalization from the nucleus to the cytoplasm \cite{Akamatsu2016}. Currently, there is an ongoing phase 2 clinical trial of perampanel,   Perampanel for Sporadic Amyotrophic Lateral Sclerosis (ALS): A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase 2 Trials,  (ClinicalTrials.gov Indentifier NCT0301941) consisting of plecebo, 4mg and 8mg per day for 48 weeks and the primary endpoint of  Change in ALS Functional rating scale.   The results are currently unavailable \cite{Aizawa2019}