Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, has long mystified the medical community and brought tremendous sorrow to those impacted by the condition. But to tell the story of ALS as one solely of tragedy would do a disservice to those who have long fought to develop an effective treatment or raise awareness. Because it is through their tireless efforts that those with ALS will eventually be able to rewrite their own ending. In today’s episode, we attempt to convey the full picture of ALS: from what we know about its causes to the earliest medical descriptions, from the baseball player whose impassioned speech captured the public’s hearts to the promising research on the horizon. Tune in for all this and more.
| History | Biology |
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| Mathis, Stéphane, et al. “When neuromuscular disorders become stars.” Journal of Neurology 272.4 (2025): 305. | Feldman, E.L., Goutman, S.A., Petri, S., Mazzini, L., Savelieff, M.G., Shaw, P.J. and Sobue, G., 2022. Amyotrophic lateral sclerosis. The Lancet, 400(10360), pp.1363-1380. |
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| Pressgrove, Geah, Brooke Weberling McKeever, and S. Mo Jang. “What is Contagious? Exploring why content goes viral on Twitter: A case study of the ALS Ice Bucket Challenge.” International Journal of Nonprofit and Voluntary Sector Marketing 23.1 (2018): e1586. | Wijesekera, L.C. and Nigel Leigh, P., 2009. Amyotrophic lateral sclerosis. Orphanet journal of rare diseases, 4(1), p.3. |
| Rowland, Lewis P. “How amyotrophic lateral sclerosis got its name: the clinical-pathologic genius of Jean-Martin Charcot.” Archives of neurology 58.3 (2001): 512-515. | Kiernan, M.C., Vucic, S., Cheah, B.C., Turner, M.R., Eisen, A., Hardiman, O., Burrell, J.R. and Zoing, M.C., 2011. Amyotrophic lateral sclerosis. The lancet, 377(9769), pp.942-955. |
| Siddique, Teepu, and Senda Ajroud-Driss. “Familial amyotrophic lateral sclerosis, a historical perspective.” Acta Myologica 30.2 (2011): 117. | Ruffo, P., Traynor, B.J. and Conforti, F.L., 2025. Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects. Journal of neurology, 272(3), p.233. |
| Sohn, Emily. “Fundraising: the ice bucket challenge delivers.” Nature 550.7676 (2017): S113-S114. | Moens, T.G., Da Cruz, S., Neumann, M., Shelkovnikova, T.A., Shneider, N.A. and Van Den Bosch, L., 2025. Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications. The Lancet Neurology, 24(2), pp.166-178. |
| Turner, Martin R., et al. “Young-onset amyotrophic lateral sclerosis: historical and other observations.” Brain 135.9 (2012): 2883-2891. | Mehta, P., Raymond, J., Nair, T., Han, M., Berry, J., Punjani, R., Larson, T., Mohidul, S. and Horton, D.K., 2025. Amyotrophic lateral sclerosis estimated prevalence cases from 2022 to 2030, data from the national ALS Registry. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 26(3-4), pp.290-295. |
| Visser, Jeldican, JMB Vianney de Jong, and Marianne de Visser. “The history of progressive muscular atrophy: syndrome or disease?.” Neurology 70.9 (2008): 723-727. | Writing Committee for the HEALEY ALS Platform Trial, Shefner, J.M., Oskarsson, B., Macklin, E.A., Chibnik, L.B., Quintana, M., Saville, B.R., Detry, M.A., Vestrucci, M., Marion, J. and McGlothlin, A., 2025. Pridopidine in amyotrophic lateral sclerosis: the HEALEY ALS platform trial. Jama, 333(13), pp.1128-1137. |
| Feldman, E.L., Goutman, S.A., Petri, S., Mazzini, L., Savelieff, M.G., Shaw, P.J. and Sobue, G., 2022. Amyotrophic lateral sclerosis. The Lancet, 400(10360), pp.1363-1380. | |
| Goutman, S.A., Savelieff, M.G., Jang, D.G., Hur, J. and Feldman, E.L., 2023. The amyotrophic lateral sclerosis exposome: recent advances and future directions. Nature Reviews Neurology, 19(10), pp.617-634. | |
| Wang, H., Guan, L. and Deng, M., 2023. Recent progress of the genetics of amyotrophic lateral sclerosis and challenges of gene therapy. Frontiers in neuroscience, 17, p.1170996. | |
| Akçimen, F., Lopez, E.R., Landers, J.E., Nath, A., Chiò, A., Chia, R. and Traynor, B.J., 2023. Amyotrophic lateral sclerosis: translating genetic discoveries into therapies. Nature Reviews Genetics, 24(9), pp.642-658. | |
| Del Aguila, M.A., Longstreth Jr, W.T., McGuire, V., Koepsell, T.D. and Van Belle, G., 2003. Prognosis in amyotrophic lateral sclerosis: a population-based study. Neurology, 60(5), pp.813-819. | |
| Amado, D.A., Robbins, A.B., Whiteman, K.R., Smith, A.R., Chillon, G., Chen, Y., Fuller, J.A., Patty, N.A., Izda, A., Cheng, C. and Nelson, S., 2025. AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 mice. Nature communications, 16(1), p.5334. | |
| Miller, T.M., Cudkowicz, M.E., Genge, A., Shaw, P.J., Sobue, G., Bucelli, R.C., Chiò, A., Van Damme, P., Ludolph, A.C., Glass, J.D. and Andrews, J.A., 2022. Trial of antisense oligonucleotide tofersen for SOD1 ALS. New England Journal of Medicine, 387(12), pp.1099-1110. | |
| Miller, T.M., Cudkowicz, M.E., Shaw, P.J., Genge, A., Sobue, G., Bucelli, R.C., Chiò, A., Van Damme, P., Ludolph, A.C., Glass, J.D. and Andrews, J.A., 2026. Long-term tofersen in SOD1 amyotrophic lateral sclerosis. JAMA neurology, 83(2), pp.115-125. |
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