Emerging clinical investigational drugs for the treatment of amyotrophic lateral sclerosis

ABSTRACT

Introduction

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.

Areas covered

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).

Expert opinion

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.

KEYWORDS:

• Amyotrophic lateral sclerosis
• new drugs
• clinical trials
• kinase inhibitors
• emerging pharmacological therapies

Article highlights

• Drug development for ALS is a very active and evolving field both in academic and private sector with 75 registered assays with active clinical research (ClinicalTrials.gov).

• The pathogenic mechanisms most targeted are neuroinflammation, proteostasis and oxidative stress, with kinase inhibitors accounting for about 30% of the investigational drugs.

• Innovative clinical research strategies, such as multitarget therapies, drug repurposing and improved clinical trial design including patient’s stratification and adaptive platform trials (APT), are being developed in order to accelerate and optimize drug development for ALS.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by La Caixa Foundation and Fundacion Luzon (grant HR21-00931) and National Health Institute ISCiii (grant CB18/05/00040, CIBERNED).