A specially appointed professor at the Center for Clinical Medicine, International University of Health and Welfare (Lecturer, Graduate School of Medicine, The University of Tokyo) and a research group at the University of Tokyo have found that there was no effective treatment for myotrophic lateral sclerosis (ALS). Announced that it has succeeded in developing a new treatment method rooted in the cause of the onset.
Amyotrophic lateral sclerosis (ALS) is a neurological intractable disease characterized by progressive weakness and muscular atrophy, and there is no effective treatment. The majority of ALS is non-hereditary sporadic ALS, and the research group found that a decrease in the enzyme ADAR2 resulted in excessive intracellular calcium influx and was involved in the death of motor neurons (motor neurons) in sporadic ALS. I found out that it was.
In sporadic ALS, AMPA receptors (a type of glutamate receptor) with abnormally high calcium permeability are expressed.Perampanel (product name "Ficompa" Eisai Co., Ltd.) is an antiepileptic drug, but it has been investigated to suppress motor neuron death because it inhibits the activation of AMPA receptors by glutamate and suppresses nerve hyperexcitability.
This time, the research group orally administered perampanel to ALS model mice for 90 consecutive days.As a result, the progression of motor dysfunction and the degenerative loss of motor neurons that caused it were stopped.Moreover, the abnormal intracellular localization of ALS-specific TDP-43 protein (TDP-43 pathology) caused by motor neurons was recovered and normalized.In addition, the progression of symptoms due to motor neuron death was suppressed not only before the onset but also after the onset.
As a result of model mice, perampanel is an approved therapeutic agent for epilepsy, and its effectiveness in mice was confirmed to be less than the dose required for epilepsy treatment when converted to humans, so the hurdle for clinical application is low. It is expected to be a specific treatment for ALS.
