Therapeutic Approaches to Amyotrophic Lateral Sclerosis from the Lab to the Clinic

Vivek   P.   Chavda; Chirag      Patel; Dharti      Modh; Yavuz   Nuri   Ertas; Shreya   S.   Sonak; Nafesa   K.   Munshi; Krishnan      Anand; Arun      Soni; Sonal      Pande
doi:10.2174/1389200223666220310113110
Abstract

Amyotrophic Lateral Sclerosis (ALS) is a terminal neuro-degenerative disorder that is clinically recognized as a gradual degeneration of the upper and lower motor neurons, with an average duration of 3 to 5 years from initial of symptoms to death. The mechanisms underlying the pathogenesis and progression of the disease are multifactorial. Therefore, to find effective treatments, it is necessary to understand the heterogeneity underlying the progression of ALS. Recent developments in gene therapy have opened a new avenue to treat this condition, especially for the characterized genetic types. Gene therapy methods have been studied in various pre-clinical settings and clinical trials, and they may be a promising path for developing an effective and safe ALS cure. A growing body of evidence demonstrates abnormalities in metabolic energy at the cellular and whole-body level in animal models and people living with ALS. Using and incorporatig high-throughput "omics" methods have radically transformed our thoughts about ALS, strengthened our understanding of the disease's dynamic molecular architecture, differentiated distinct patient subtypes, and created a reasonable basis for identifying biomarkers and novel individualised treatments. Future clinical and laboratory trials would also focus on the diverse relationships between metabolism and ALS to address the issue of whether targeting poor metabolism in ALS is an effective way to change disease progression. In this review, we focus on the detailed pathogenesis of ALS and highlight principal genes, i.e., SOD1, TDP-43, C9orf72, and FUS, as well as targeted ALS therapies. An attempt is made to provide up-to-date clinical outcomes, including various biomarkers that are thought to be important players in early ALS detection.
Keywords: Amyotrophic lateral sclerosis, SOD1, TDP-43, FUS, biomarkers, treatment, clinical trials.
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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1389200223666220310113110	Print ISSN 1389-2002
Publisher Name Bentham Science Publisher	Online ISSN 1875-5453
Current Drug Metabolism

Therapeutic Approaches to Amyotrophic Lateral Sclerosis from the Lab to the Clinic

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