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

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 initiation 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 this 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 a variety of 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 energy metabolism at the cellular and whole-body level in animal models and in people living with ALS. The use and incorporation of high-throughput "omics" methods has radically transformed our thought about ALS, strengthening our understanding of the disease's dynamic molecular architecture, differentiating distinct patient subtypes, and creating a reasonable basis for the identification of 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 deficient 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, targeted therapeutic approaches of ALS. An attempt is made to provide up-to-date information on clinical outcomes, including various biomarkers which are thought to be important players in early ALS detection.

A Comprehensive Review of Secondary Movement Disorders

“…Amyotrophic lateral sclerosis (ALS), also known as Lou disease, is a neurodegenerative disorder that affects the motor neurons in the brain and spinal cord [112]. ALS leads to progressive muscle weakness and atrophy, eventually affecting the ability to move, speak, swallow, and breathe.…”

Recent Advances in the Study of Na+/K+-ATPase in Neurodegenerative Diseases

“…Disturbing cell death pathways slows the development of HD. However, it is difficult to rescue neuronal loss in HD [ 110 ]. It is interesting to observe that NKA dysfunction promotes neuronal loss via different mechanisms.…”