Ethnical Disparities in Response to Edaravone in Patients With Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a progressive neurodegenerative disease characterized by the weakness of voluntary muscles due to the loss of motor neurons. Symptoms ultimately culminate in the form of respiratory failure due to the involvement of the diaphragm. Unfortunately, there is no known cure for this disease. Hence, supportive therapy is the only available option in most terminal cases. However, Riluzole and Edaravone (EDA) are the only two known drugs approved by the U.S. Food and Drug Administration (FDA) for treating this condition. In 2017, EDA was approved for the treatment of ALS. It is hypothesized that Riluzole and EDA work via a mechanism involving antioxidants, which nullifies the oxidative stress believed to be involved in ALS. However, most studies in several countries have found a wide range of disparities in the efficacy of this drug. In this review, we aim to summarize the differences in results from epidemiological studies across 10 different countries and hypothesize the potential causes of these differences.

Keywords: als; amyotrophic lateral sclerosis; edaravone; ethnicity; genetics; motor neuron disease; motor neurons; neurodegenerative disease; neurodegenerative disorders; riluzole.

Figure 1. Mechanisms of Action of EDA

H2O2: hydrogen peroxide; ATP: adenosine triphosphate; Nrf2: nuclear factor-erythroid factor 2-related factor 2; PFN-1: profilin-1; EDA: edaravone Original figure, made by author Maleesha Jayasinghe