A place for US healthcare professionals interested in learning more about the rapidly changing science of genetic ALS, featuring content co-created with key medical experts in the field.
SPONSORED BY BIOGEN AND OFFERED THROUGH INVITAE
Biogen-sponsored genetic testing offered through Invitae includes more than 20 ALS-associated genes.
ALS is a rare, fatal, neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord.1 Onset of ALS is usually between the ages of 40 to 70, with the average age at diagnosis being 55 years. Unfortunately, typical life expectancy following diagnosis is only 3 to 5 years.1,2 ALS is a complex disease likely underpinned by the presence of different pathogenic mechanisms, including multiple genetic factors.2
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The discovery and investigation of these genes hold great promise for a better understanding of genetic ALS and disease management in the future.
Superoxide dismutase 1 (SOD1), discovered in 1993, was the first gene discovered to be associated with ALS.9 SOD1 accounts for approximately 15% of fALS patients and has been found in ~1% of sALS patients.10 Chromosome 9 open reading frame 72 (C9orf72), discovered in 2011,7 accounts for approximately 33% of identified fALS patients and has been found to account for ~5% of sALS patients.10 These 2 genes are the most common gene mutations in genetic ALS, but there are many others, including TARDBP (~3.3% for fALS and ~0.5% for sALS), and FUS (~3.0% for fALS and ~0.4% for sALS).*10,11
*based on global population data.
Whole-genome or exome sequencing technology has assisted researchers in identifying more than 25 genes associated with familial ALS cases.2
Estimates of percentages are from European sources.
Although genetic testing is often limited to patients with a family history of ALS, research shows ~10% of sporadic ALS may have a genetic cause.6,12
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Genetic testing for all ALS patients may help provide a better understanding of the basis of their condition, allowing accurate risk assessment and a more comprehensive healthcare decisions and life choices.8 Clinical trials specific to genetic forms of ALS offer a reason to discover which ALS-associated mutation(s) a patient may carry.
Even though the percentage of sALS cases with a genetic component is smaller than fALS cases (approximately 10% of sALS cases compared to ~70% of fALS cases), their total number may account for the majority of ALS cases associated with genetic causation. This is because sALS cases make up about 90-95% of all ALS cases.4–7
1. Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis. NEJM. 2017; 377: 162-72.
2. Nguyen HP, Van Broeckhoven C, van der Zee J. ALS Genes in the Genomic Era and their Implications for FTD. Trends Genet. 2018;34(6):404-423.
3. Renton AE, Chiò A, Traynor BJ. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci 2014;17(1):17-23.
4. Zarei S, Carr K, Reiley L, et al. A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int. 2015;6:171.
5. Byrne S, Walsh C, Lynch C, et al. Rate of familial amyotrophic lateral sclerosis: a systemic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2011;82:623-627.
6. Volk E, Weishaupt JH, Andersen PM, et al. Current knowledge, and recent insights into the genetic basis of amyotrophic lateral sclerosis. Medgen. 2018;30:252-258.
7. Arthur KC, Calvo A, Price TR, et al. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040. Nat Commun. 2016;7:12408.
8. Roggenbuck J, Quick A, Kolb SJ. Genetic testing and genetic counseling for amyotrophic lateral sclerosis: an update for clinicians. Genet Med. 2017;19(3):267-274.
9. Rosen DR. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;364(6435):362.
10. Zou ZY, Zhou ZR, Che CH, et al. Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2017;88(7):540-549.
11. Bali T, Self W, Liu J, et al. Defining SOD1 ALS natural history to guide therapeutic clinical trial design. J Neurol Neurosurg Psychiatry. 2017;88(2):99-105.
12. Vajda A, McLaughlin RL, Heverin M, et al. Genetic testing in ALS: A survey of current practices. Neurology. 2017;88(10):991-999.
13. Bunton-Stasyshyn RK, Saccon RA, Fratta P, et al. SOD1 Function and Its Implications for Amyotrophic Lateral Sclerosis Pathology: New and Renascent Themes. Neuroscientist. 2015;21(5):519-529.
14. Robberecht W, Philips T. The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci. 2013.
15. Leko MB, Zupunski V, Kirincich J, et al. Moleucular mechanisms of neurodegeneration related to C9orf72 hexanucleotide repeat expansion. Hindawi. Behavioural Neurology. 2019: 1-18.