[Perampanel for Sporadic Amyotrophic Lateral Sclerosis]

Area of Science:

• Neuroscience
• RNA Biology
• Pharmacology

Background:

• Sporadic amyotrophic lateral sclerosis (sALS) is linked to reduced adenosine deaminase acting on RNA 2 (ADAR2) in motor neurons.
• ADAR2 deficiency impairs calcium (Ca2+) regulation in motor neurons by affecting AMPA receptors, potentially causing TDP-43 pathology and neuronal death.
• AMPA receptor antagonists are hypothesized to prevent excessive Ca2+ influx and motor neuron degeneration in sALS.

Purpose of the Study:

• To evaluate the therapeutic potential of perampanel, an AMPA receptor antagonist, in patients with sporadic amyotrophic lateral sclerosis (sALS).
• To investigate if perampanel can mitigate motor neuron degeneration by blocking excessive Ca2+ influx associated with ADAR2 deficiency.

Main Methods:

• A multicenter, randomized, double-blinded, placebo-controlled, parallel-group phase 2 clinical trial was conducted.
• Participants received either perampanel or a placebo for 48 weeks.
• The primary outcome measure was the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score over the treatment period.

Main Results:

• Results of the phase 2 clinical trial are anticipated in early 2020.
• The study aimed to determine the efficacy of perampanel in improving functional outcomes for sALS patients.

Conclusions:

• Perampanel demonstrates therapeutic potential for sALS based on preclinical studies in mouse models.
• This clinical trial will provide crucial data on the safety and efficacy of perampanel as a treatment for sporadic ALS.