ABSTRACT
Finding a cure for ALS is the goal of all ALS research. Recent decades have seen remarkable progress in all stages of drug development: basic laboratory research has elucidated steps in the cascade leading to motor neuron death and thus identified molecular targets for experimental treatment. Transgenic animal research has resulted in several models of ALS, facilitating preclinical testing of candidate drugs. Finally, clinical research has refined outcome measures and trial design. This allows for valid clinical experiments to assess the efficacy of new ALS treatments. Despite the remarkable progress in all areas of preclinical and clinical drug development, the glutamate antagonist riluzole remains the only drug approved by the Food and Drug Administration (FDA) for the treatment of ALS. This chapter provides an overview of riluzole’s path to approval and of its impact on ALS care. This is followed by a discussion of recent randomized, controlled clinical trials in ALS. The series of negative trials that has followed riluzole’s success has raised a fundamental question: Do the drugs tested truly lack benefit in ALS or have the clinical trials designed to evaluate them just failed to demonstrate their benefit? This chapter discusses the limitations and accomplishments of recent ALS trials. It is always easy to raise issues with hindsight. The intent of this chapter is not to be critical of specific ALS trials, but rather to constructively discuss what lessons could be learned from the accumulating experience.
