Emerging therapies for amyotrophic lateral sclerosis applied to drug discovery

Abstract

Background: Amyotrophic Lateral Sclerosis (ALS) is a progressive neuromuscular disease mainly caused by genetic disorders. This progressive disorder involves the degeneration of motor neurons at various levels. Drugs have been studied, and they show improvement in survival and reduced progression of the disease, they are riluzole and edaravone. Objectives: Investigate emerging therapies for the treatment of ALS. Methods: The Pubmed database was used to conduct the research, and the keywords were “Amyotrophic Lateral Sclerosis”, “Emerging”, “Therapies”,”Drugs”, all present in Mesh. Articles from 2016 to 2021 were used. And the survey was conducted on May 2, 2021. Results: Only two drugs have been approved yet by the Food and Drug Administration for the treatment of ALS, riluzole and edaravone, and each one offers modest benefits in mortality and/or function. On the other hand, 88 studies of clinical intervention trials are active using different drugs. Current therapies under development include oral tyrosine kinase inhibitors (masitinib, trametinib); the antisense oligonucleotide (tofersen); the human monoclonal antibody inhibitor (ravulizumab); and mesenchymal stem cells (MSC); among others (RT001, Enoxacin, Engensis, ANX005, Deferiprone). Conclusions: Due to gaps in the knowledge of the specific pathophysiology of ALS, the definitive treatment is still a mystery. The drugs currently in use, riluzole and edaravone, are the most promising in terms of delaying the progression of the disease.

Dextromethorphan/quinidine for the treatment of bulbar impairment in amyotrophic lateral sclerosis

“…This includes compensatory approaches such as dietary and environmental modifications, feeding tube placement, and alternative and assistive communication interventions that are implemented reactively once dysarthria or dysphagia manifest and are clinically detected. 7,8 The lack of targeted treatment options to proactively improve or maintain bulbar function represents a crucial clinical management gap in the care of pALS. [9][10][11] To date, no efficacious treatments have been identified to prolong safe and efficient oral intake or functional communication in pALS.…”

“…[9][10][11] To date, no efficacious treatments have been identified to prolong safe and efficient oral intake or functional communication in pALS. 7 The need for clinical trials to improve treatment options and bulbar symptom management for pALS has been called for by the Northeastern ALS (NEALS) Consortium Bulbar Subcommittee. 12 Recent excitement has surfaced regarding the therapeutic potential of a pharmacologic intervention, Nuedexta (20 mg dextromethorphan HBr/10 mg quinidine sulfate, DMQ), for the treatment of bulbar dysfunction in pALS.…”