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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder caused by motoneuron death with a median survival time of 3–5 years since disease onset. There are no effective treatments to date. However, a variety of innovative investigational drugs and biological-based therapies are under clinical development. This review provides an overview of the clinical investigational small molecules as well as a brief summary of the biological-based therapies that are currently undergoing clinical trials for the treatment of ALS. All the data were obtained from ClinicalTrials.gov (registered through November 1). Drug discovery for ALS is an active and evolving field, where many investigational clinical drugs are in different trials. There are several mechanisms of action supporting all these new therapies, although proteostasis is gaining stage. Probably, small orally bioavailable molecules able to recover functional TDP-43 homeostasis may have solid chances to modify ALS progression.

Emerging clinical investigational drugs for the treatment of amyotrophic lateral sclerosis