Leevi
ALStuttu:n jäsen
Oheisessa tutkimuksessa tutkijat osoittivat että suun kautta annosteltu perampaneeli, AMPA-reseptorien antagonisti esti merkittävästi ALS:n etenemistä ja normalisoi TDP-43 patologiaan liittyvää motoneuronien tuhoutumista AR2-hiirillä. Perampaneeli on hyväksytty epilepsialääke, joka on myös potentiaalinen ALS-lääke ja tutkijoiden mukaan ansaitsee kliinisen kokeen.
http://www.ncbi.nlm.nih.gov/pubmed/27350567
Sci Rep. 2016 Jun 28;6:28649. doi: 10.1038/srep28649.
The AMPA receptor antagonist perampanel robustly rescues amyotrophic lateral sclerosis (ALS) pathology in sporadic ALS model mice.
Akamatsu M1,2, Yamashita T1,2, Hirose N1,2, Teramoto S1,2, Kwak S1,3.
Abstract
Both TDP-43 pathology and failure of RNA editing of AMPA receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of the majority of patients with amyotrophic lateral sclerosis (ALS). AR2 mice, in which an RNA editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) is conditionally knocked out in the motor neurons, exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons through a Ca(2+)-permeable AMPA receptor-mediated mechanism. Therefore, amelioration of the increased Ca(2+) influx by AMPA receptor antagonists may be a potential ALS therapy. Here, we showed that orally administered perampanel, a selective, non-competitive AMPA receptor antagonist significantly prevented the progression of the ALS phenotype and normalized the TDP-43 pathology-associated death of motor neurons in the AR2 mice. Given that perampanel is an approved anti-epileptic drug, perampanel is a potential candidate ALS drug worthy of a clinical trial.
http://www.ncbi.nlm.nih.gov/pubmed/27350567
Sci Rep. 2016 Jun 28;6:28649. doi: 10.1038/srep28649.
The AMPA receptor antagonist perampanel robustly rescues amyotrophic lateral sclerosis (ALS) pathology in sporadic ALS model mice.
Akamatsu M1,2, Yamashita T1,2, Hirose N1,2, Teramoto S1,2, Kwak S1,3.
Abstract
Both TDP-43 pathology and failure of RNA editing of AMPA receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of the majority of patients with amyotrophic lateral sclerosis (ALS). AR2 mice, in which an RNA editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) is conditionally knocked out in the motor neurons, exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons through a Ca(2+)-permeable AMPA receptor-mediated mechanism. Therefore, amelioration of the increased Ca(2+) influx by AMPA receptor antagonists may be a potential ALS therapy. Here, we showed that orally administered perampanel, a selective, non-competitive AMPA receptor antagonist significantly prevented the progression of the ALS phenotype and normalized the TDP-43 pathology-associated death of motor neurons in the AR2 mice. Given that perampanel is an approved anti-epileptic drug, perampanel is a potential candidate ALS drug worthy of a clinical trial.