PT - JOURNAL ARTICLE AU - Megumi Akamatsu AU - Takenari Yamashita AU - Sayaka Teramoto AU - Zhen Huang AU - Janet Lynch AU - Tatsushi Toda AU - Li Niu AU - Shin Kwak TI - Testing of the therapeutic efficacy and safety of AMPA receptor RNA aptamers in an ALS mouse model AID - 10.26508/lsa.202101193 DP - 2022 Apr 01 TA - Life Science Alliance PG - e202101193 VI - 5 IP - 4 4099 - https://www.life-science-alliance.org/content/5/4/e202101193.short 4100 - https://www.life-science-alliance.org/content/5/4/e202101193.full SO - Life Sci. Alliance2022 Apr 01; 5 AB - In motor neurons of sporadic amyotrophic lateral sclerosis (ALS) patients, the RNA editing at the glutamine/arginine site of the GluA2 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors is defective or incomplete. As a result, AMPA receptors containing the abnormally expressed, unedited isoform of GluA2 are highly Ca2+-permeable, and are responsible for mediating abnormal Ca2+ influx, thereby triggering motor neuron degeneration and cell death. Thus, blocking the AMPA receptor–mediated, abnormal Ca2+ influx is a potential therapeutic strategy for treatment of sporadic ALS. Here, we report a study of the efficacy and safety of two RNA aptamers targeting AMPA receptors on the ALS phenotype of AR2 mice. A 12-wk continuous, intracerebroventricular infusion of aptamers to AR2 mice reduced the progression of motor dysfunction, normalized TDP-43 mislocalization, and prevented death of motor neurons. Our results demonstrate that the use of AMPA receptor aptamers as a novel class of AMPA receptor antagonists is a promising strategy for developing an ALS treatment approach.