RT Journal Article
SR Electronic
T1 Testing of the therapeutic efficacy and safety of AMPA receptor RNA aptamers in an ALS mouse model
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101193
DO 10.26508/lsa.202101193
VO 5
IS 4
A1 Megumi Akamatsu
A1 Takenari Yamashita
A1 Sayaka Teramoto
A1 Zhen Huang
A1 Janet Lynch
A1 Tatsushi Toda
A1 Li Niu
A1 Shin Kwak
YR 2022
UL https://www.life-science-alliance.org/content/5/4/e202101193.abstract
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.