Amyotrophic Lateral Sclerosis (ALS), is a devastating neurodegenerative disorder, overlapping with Fronto-temporal Dementia (FTD), and is part of a series of syndromes defined as Motor Neuron Diseases (MND) that is characterized by the progressive loss of motor neurons in the brain and spinal cord[1]. The exact pathology is still unclear, but mechanisms such as mitochondrial dysfunction, oxidative stress, inflammation, and glutamate overload are thought to contribute to neuronal loss[2]. ALS is classified based on the initial symptoms: Limb-Onset ALS, and Bulbar-Onset ALS. Over time, ALS often progresses to involve both limb and bulbar regions, causing widespread motor function issues. The disease is also categorized into familial (10%) and sporadic (90%) cases[3], the distinction between limb-onset and bulbar-onset ALS is not strongly associated with the sporadic or familial nature of the disease. The diversity of genetic factors emphasizes the complexity of ALS-FTD, with over 30 identified genes contributing to ALS, including C9ORF72, the most common genetic cause, SOD1, TARDBP, and FUS[4]. The exact pathology causes of ALS is mostly unknown. In some cases, there is some evidence of inflammation in the gut at early stages in the disease and a change (dysbiosis) in the gut microbiota may also contribute to disease progression[5]. The median survival from the onset of symptoms is approximately 3.5 years, although there are cases of patients living beyond 5 years[6], with the rapid progression of the disease, impacting the quality of life (QoL) of the patients and their families. It is considered a rare disease, affecting 32,000 people in Europe[7] and resulting in 10,000 deaths a year. ALS faces distinct treatment landscapes in Europe and the United States. In Europe, Riluzole (Rilutek) is the sole approved drug. In the USA, a broader array of treatments is approved but none which provide any significant extension in lifespan. Hope lies in ongoing research and transformative breakthroughs are needed to have any significant impact on for the ALS patient.
[1] Feldman, E. L., Goutman, S. A., Petri, S., Mazzini, L., Savelieff, M. G., Shaw, P. J., & Sobue, G. (2022). Amyotrophic lateral sclerosis.
[2] Lee Albert J. B., Kittel Tyler E., Kim Renaid B., Bach Thao-Nguyen, Zhang Tian, Mitchell Cassie S. (2023) Comparing therapeutic modulators of the SOD1 G93A Amyotrophic Lateral Sclerosis mouse pathophysiology.
[3] Kim G, Gautier O, Tassoni-Tsuchida E, Ma XR, Gitler AD. (2020) ALS Genetics: Gains, Losses, and Implications for Future Therapies. Neuron.
[4] Suzuki, N., Nishiyama, A., Warita, H. et al. (2023) Genetics of amyotrophic lateral sclerosis: seeking therapeutic targets in the era of gene therapy.
[5] Hong D, Zhang C, Wu W, Lu X, Zhang L. (2023) Modulation of the gut-brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis.
[6] Alcaz S, Jarebinski M, Pekmezović T, Marinković Z, Apostolski S. (1997) Survival in amyotrophic lateral sclerosis]. Srp Arh Celok Lek.
[7] Brown CA, Lally C, Kupelian V, Flanders WD. (2021) Estimated Prevalence and Incidence of Amyotrophic Lateral Sclerosis and SOD1 and C9orf72 Genetic Variants.