Riluzole does not improve lifespan or motor function in three ALS mouse models.

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Riluzole is the primary FDA-approved drug for amyotrophic lateral sclerosis (ALS).
• Its efficacy has been questioned due to its approval before the development of relevant animal models.
• This study evaluates riluzole in three distinct ALS mouse models.

Purpose of the Study:

• To assess the efficacy of riluzole in preclinical amyotrophic lateral sclerosis (ALS) mouse models.
• To determine if riluzole impacts lifespan and motor function decline in these models.

Main Methods:

• Three transgenic mouse models of ALS (SOD1^G93A, TDP-43^A315T, FUS (1-359)) were used.
• Mice received riluzole (22 mg/kg) or vehicle in drinking water from symptom onset.
• Lifespan and motor function (Rotarod, stride length) were monitored.

Main Results:

• Riluzole treatment did not significantly improve lifespan in any of the tested ALS mouse models.
• No significant impact on motor performance decline was observed in FUS (1-359) and SOD1^G93A mice.
• The TDP-43^A315T model's response to riluzole was not detailed in the provided results.

Conclusions:

• Current data suggest riluzole would not pass preclinical assessment if evaluated today.
• The findings raise concerns regarding the standards for preclinical evaluation of ALS therapeutics.
• Re-evaluation of riluzole's efficacy in light of modern preclinical models is warranted.