• ALS in a neurodegenerative disease
  • So far the disease has no cure, only symptomatic treatment
  • The new research will help the patients reduce the symptoms, and push for further studies

Introduction – Amyotrophic lateral sclerosis is a disease that attacks the neurons, in the nervous system, that control the skeletal muscles (1). The people affected develop weakness in arms or legs, stiff muscles and muscle twitching. As the disease advances patients present with difficulty in breathing and swallowing.

Mechanism of neuron degeneration – The exact cause of ALS is not known but both genetic and environmental factors are involved (2) . There are more than 20 genes involved in familial ALS, including C9orf72 (40%), SOD1 (20%), FUS (1–5%), and TARDBP (1–5%)(3). These genes are categorized into three groups: 1. protein degeneration, 2. cytoskeleton deformation, 3. RNA processing. C9orf72 is the most commonly mutated gene in ALS and causes motor neuron death through a number of mechanisms(4). The mutation that is thought to cause this pathology is the repetition of a hexanucleotide –GGGGCC, over and over (5). How this repetition induces cell pathology is by deposition of RNA transcripts in the nucleus, translation of the RNA into toxic dipeptide repeat proteins in the cytoplasm, and decreased levels of the normal C9orf72 protein (6). The hallmark in pathology for ALS are inclusion bodies in the cytoplasm of neurons (7). The protein build-up in the neurons is toxic and causes neuronal cell death to both the upper motor neurons and the lower motor neurons.

Fig. 1.) Scheme of all the pathways that are thought to cause cell death in e neuron. Image adapted from (8)

Treatment – The disease has no cure, so management includes treatment of symptoms, supportive care and improvement of life quality.

  • Edaravone or riluzole are the treatments recommended for the symptoms.
  • Physical therapy is recommended to delay the muscle atrophy.
  • Non invasive ventilation is used in case of need for the patients with advanced ALS (9) .

Latest research – The researchers discovered that the proteins coded by the C9orf72 gene are translated by a process called repeat-associated non-AUG (RAN), which allows the proteins to build up without control. Throughout the research it was understood that other genes allowed for this build up, when their activity was increased. more specifically the gene RPS25. The study was done on yeast and fruit flies, which are species where genes can be controlled very easily. When the scientists reduced the activity of the RPS25 gene, the number of proteins was lowered. (10)

Fig. 2.) Mechanisms of action on how the C9orf72 gene causes protein build-up toxicity. Image adapted from (11)

Conclusion – The point of this study is to find ways to treat ALS and to reduce symptoms. This research has given information about the genetic components of the disease that, we do not yet understand. However, this is progress in the genetic treatment of the disease. This will set forth new research on the genetic treatment of ALS to help detect and treat these patients as early as possible.

COPYRIGHT: This article is the property of We Speak Science, a non-profit institution co-founded by Dr. Detina Zalli and Dr. Argita Zalli. The article is written by  Arrita Beqa, University of Prishtina, Kosovo.


1. “Amyotrophic Lateral Sclerosis (ALS) Fact Sheet”. National Institute of Neurological Disorders and Stroke.

2. Wingo TS, Cutler DJ, Yarab N, Kelly CM, Glass JD (2011). “The heritability of amyotrophic lateral sclerosis in a clinically ascertained United States research registry”. PLOS One. 6 (11): e27985. Bibcode:2011PLoSO…627985W. doi:10.1371/journal.pone.0027985. PMC 3222666. PMID 2 2132186.

3. van Es MA, Hardiman O, Chio A, Al-Chalabi A, Pasterkamp RJ, Veldink JH, van den Berg LH (November 2017). “Amyotrophic lateral sclerosis”. Lancet. 390 (10107): 2084– 2098. doi:10.1016/S0140-6736(17)31287-4. PMID 28552366.

4. Brown RH, Al-Chalabi A (13 July 2017). “Amyotrophic Lateral Sclerosis”. The New England Journal of Medicine. 377 (2): 162–172.

5. Nguyen HP, Van Broeckhoven C, van der Zee J (June 2018). “ALS Genes in the Genomic Era and their Implications for FTD”. Trends in Genetics.

6. Brown RH, Al-Chalabi A (13 July 2017). “Amyotrophic Lateral Sclerosis”. The New England Journal of Medicine.

7. Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, van den Berg LH (October 2017). “Amyotrophic lateral sclerosis”. Nature Reviews. Disease Primers.

8. Philip Van Damme P, Robberecht W, Van Den Bosch L (May 2017). “Modelling amyotrophic lateral sclerosis: progress and possibilities”. Disease Models and Mechanisms.

9. Abe K, Masashi A, Tsuji S, Itoyama Y, Sobue G, Togo M, et al. (July 2017). “Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial”. The Lancet. Neurology.

10. https://www.popsci.com/lou-gehrig-als-brain-gene-protein/

11. https://www.researchgate.net/figure/C9orf72-mutations-three-proposed-pathomechanisms-A-TheC9orf72-gene-harbors-a_fig1_301203438