Author Archives: Biogen

Perspective from Christopher McDermott, MBChB, FRCP, PhD Professor Chris McDermott is a professor and neurologist at SITraN in the UK (Sheffield Institute for Translational Neuroscience), a leading center for the study of ALS. Professor McDermott is a paid consultant for Biogen and was compensated for this article. Early in my clinical practice, my team and I subscribed to the traditional view of ALS: the disease was either familial or sporadic. People with "familial" ALS had some family history of ALS (and therefore a possible genetic component), while people with "sporadic" disease did not have a family history.1 But that view began to change with the discovery that mutations (or changes) in a gene called C9orf72 could play a role in both the sporadic and familial types of ALS. Over time, we learned that this one mutation accounted for approximately 40% of familial ALS cases. Even more surprising: it accounted for close to 10% of cases in people with no family history of ALS—people previously believed to have the sporadic form of the disease. As this story unfolded, we began to question our old assumptions about familial and sporadic ALS, and we realized that just asking our patients about their family history wasn’t enough. C9orf72 has been associated with other neurologic diseases as well, so now, I and other ALS specialists understood that someone with a family history of related conditions might also have a genetic cause for their ALS. At the same time, other genetic mutations were being found in people with no family history of the disease and whose ALS had seemingly appeared out of nowhere.1 It was becoming clear that some people with what we often referred to as sporadic ALS could actually have a genetic component to their disease.1 My own research supported this belief. The Sheffield Institute for Translational Neuroscience, where we help develop and study new therapies for neuromuscular diseases, had an extensive biobank of samples from people with ALS. As new genetic mutations were discovered, our researchers tested these samples and found that many people who we thought had sporadic ALS in fact had one or more genetic mutations. In other words, many people with seemingly sporadic ALS actually had genetic forms of the disease. With time, it became clear to me that there were more ALS cases with a genetic cause than we realized at first.4 Genetic testing is key to understanding ALS1 I’ve begun to make genetic testing a standard part of my diagnostic workup for all of my patients with ALS. In the past, I used to steer these same patients away from genetic testing because I thought there was little to be learned from it—but things have changed.1 I have found that many neurologists who specialize in ALS now embrace systematic genetic testing when they start to diagnose their patients. It is my firm belief that these tests have something to offer each patient, whether they have a family history of ALS or not. In addition to informing a more complete picture of each individual case, I feel that genetic testing broadens our understanding of ALS as a whole. It is also helpful for people living with the disease and their families, who might have questions about their disease, prognosis, family planning, and potential clinical trial participation.1,5 Genetic discoveries may help to inform clinical trial participation1,5,6 Knowing more about which mutation a person has helps in identifying clinical trials that are specific to their form of the disease.1,5,6 I really have a sense that, hopefully within my career, genetic ALS will become a disease that's understood and approached very differently. As we gain a better understanding of the genetic mutations associated with ALS, we will hopefully see clinical trials that include people with those mutations. This may lead to a greater understanding of genetic ALS.1,5,6 I also envision that genetic testing will become common practice in the future, and clinical practices will include a genetic counselor as part of a multidisciplinary team. As in other areas of medicine where genetics already play a role, I believe there will be a process to support patients in their understanding of the possible genetic basis for their ALS diagnosis. Want to learn more about genetic ALS? Visit insideALS.com from Biogen to find helpful articles, videos, and insights from ALS experts. References 1. 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. 2. Kaufman DJ, Murphy-Bollinger J, Scott J, Hudson KL. Public opinion about the importance of privacy in biobank research. Am J Hum Genet. 2009;85(5):643-654. 3. Parodi B. Biobanks: A definition. In: Mascalzoni D, ed. Ethics, Law and Governance of Biobanking. The International Library of Ethics, Law and Technology, vol 14. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9573-9_2 4. Boylan K. Familial amyotrophic lateral sclerosis. Neurol Clin. 2015;33(4):807-830. 5. Benatar M, Stanislaw C, Reyes E, et al. Presymptomatic ALS genetic counseling and testing: experience and recommendations. Neurology. 2016;86(24):2295-2302. 6. 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. 7. Arthur KC, Calvo A, Price TR, Geiger JT, Chiò A, Traynor BJ. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040. Nat Commun. 2016;7:12408. 8. Renton AE, Chiò A, Traynor BJ. State of play in amyotrophic lateral sclerosis. Nat Neurosci. 2014;17(1):17-23. ©2021 Biogen. All rights reserved. 225 Binney Street, Cambridge, MA 02142 05/21 ALS-US-0043

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Author Archives: Biogen

Genetic ALS: Evolving knowledge–and impact

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