Figure 8.

Mechanism-Based strategy for amyotrophic lateral sclerosis (ALS) therapy. Both gene therapy using adeno-associated virus as a vector (AAV9-ADAR2 gene therapy) and treatment with perampanel significantly prevented the progression of ALS phenotypes in conditional adenosine deaminase acting on RNA 2 (ADAR2) knockout mice (AR2) by preventing transactive response DNA-binding protein (TDP-43) pathology-associated motor neuron death. Since perampanel has already been approved as an anti-epileptic drug, robust beneficial effects on the AR2 mice in these studies suggest that perampanel, ideally in combination with ADAR2 gene therapy, would be a promising therapy for ALS. AMPAR = α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor.