Title:Therapeutic Approaches to Amyotrophic Lateral Sclerosis from the Lab to the Clinic
Volume: 23
Issue: 3
Author(s): Vivek P. Chavda*, Chirag Patel, Dharti Modh, Yavuz Nuri Ertas, Shreya S. Sonak, Nafesa K. Munshi, Krishnan Anand*, Arun Soni and Sonal Pande
Affiliation:
- Department of Pharmaceutic and Pharmaceutical Technology, LM College of Pharmacy, Ahmedabad - 380009, India
- Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences and National Health Laboratory Service, University of the Free State, Bloemfontein 9300, South Africa
Keywords:
Amyotrophic lateral sclerosis, SOD1, TDP-43, FUS, biomarkers, treatment, clinical trials.
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.