The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Phase 1–2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS
Open accessAbstract
BACKGROUND: mutations. METHODS: mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned in a 3:1 ratio to receive five doses of tofersen or placebo, administered intrathecally for 12 weeks. The primary outcomes were safety and pharmacokinetics. The secondary outcome was the change from baseline in the cerebrospinal fluid (CSF) SOD1 concentration at day 85. Clinical function and vital capacity were measured. RESULTS: A total of 50 participants underwent randomization and were included in the analyses; 48 participants received all five planned doses. Lumbar puncture-related adverse events were observed in most participants. Elevations in CSF white-cell count and protein were reported as adverse events in 4 and 5 participants, respectively, who received tofersen. Among participants who received tofersen, one died from pulmonary embolus on day 137, and one from respiratory failure on day 152; one participant in the placebo group died from respiratory failure on day 52. The difference at day 85 in the change from baseline in the CSF SOD1 concentration between the tofersen groups and the placebo group was 2 percentage points (95% confidence interval [CI], -18 to 27) for the 20-mg dose, -25 percentage points (95% CI, -40 to -5) for the 40-mg dose, -19 percentage points (95% CI, -35 to 2) for the 60-mg dose, and -33 percentage points (95% CI, -47 to -16) for the 100-mg dose. CONCLUSIONS: mutations, CSF SOD1 concentrations decreased at the highest concentration of tofersen administered intrathecally over a period of 12 weeks. CSF pleocytosis occurred in some participants receiving tofersen. Lumbar puncture-related adverse events were observed in most participants. (Funded by Biogen; ClinicalTrials.gov number, NCT02623699; EudraCT number, 2015-004098-33.).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“ASO injection is a current standard of care for the fatal childhood disease spinal muscular atrophy15 and is in five ongoing Phase I trials in ALS, Parkinson’s, and Alzheimer’s diseases and in Phase III trials for inherited ALS from a mutation in superoxide dismutase16,17 and for Huntington’s disease18.”
From Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB (2021) · cites this paper as [17]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Experience from Alzheimer’s disease (AD), spinal muscular atrophy (SMA),5 and amyotrophic lateral sclerosis (ALS)6 suggests treating FTD will be most successful if treatment is initiated early in the disease course, ideally prior to the onset of symptoms.”
From Temporal order of clinical and biomarker changes in familial frontotemporal dementia (2022) · cites this paper as [6]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy
Finkel, R. S., Mercuri, E., Darras, B. T., Connolly, A. M., Kuntz, N. L., Kirschner, J., Chiriboga, C. A., Saito, K., Servais, L., Tizzano, E., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1702752 · Cited by 2,337
Self-citationNusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy
Mercuri, E., Darras, B. T., Chiriboga, C. A., Day, J. W., Campbell, C., Connolly, A. M., Iannaccone, S. T., Kirschner, J., Kuntz, N. L., Saito, K., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1710504 · Cited by 1,433
Self-citationNon–cell autonomous toxicity in neurodegenerative disorders: ALS and beyond
Ilieva, H., Polymenidou, M., & Cleveland, D. W. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200908164 · Cited by 1,008
Antisense oligonucleotides: the next frontier for treatment of neurological disorders
Rinaldi, C., & Wood, M. J. A. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.148 · Cited by 788
Epidemiology of mutations in superoxide dismutase in amyotrophic lateal sclerosis
Cudkowicz, M., McKenna‐Yasek, D., Sapp, P. C., Chin, W., Geller, B. A., Hayden, D. L., Schoenfeld, D., Hosler, B. A., Horvitz, H. R., & Brown, R. H. (1997) · Annals of Neurology · doi:10.1002/ana.410410212 · Cited by 533
Self-citationAntisense oligonucleotide therapy for neurodegenerative disease
Smith, R. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25424 · Cited by 506
ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics
Abel, O., Powell, J. F., Andersen, P. M., & Al‐Chalabi, A. (2012) · Human Mutation · doi:10.1002/humu.22157 · Cited by 341
Self-citationIs SOD1 loss of function involved in amyotrophic lateral sclerosis?
Saccon, R. A., Bunton-Stasyshyn, R. K. A., Fisher, E., & Fratta, P. (2013) · Brain · doi:10.1093/brain/awt097 · Cited by 339
Andersen, P. M., Nilsson, P., Ala‐Hurula, V., Keränen, M.-L., Tarvainen, I., Haltia, T., Nilsson, L., Binzer, M., Forsgren, L., & Marklund, S. L. (1995) · Nature Genetics · doi:10.1038/ng0595-61 · Cited by 323
Self-citationAndersen, P. M. (1997) · Brain · doi:10.1093/brain/120.10.1723 · Cited by 301
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–300 of 565
Nucleic acid-based therapeutics for the treatment of central nervous system disorders
McCartan, R., Khorkova, O., Volmar, C., & Wahlestedt, C. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1250276 · Cited by 22
“Tofersen functions by mediating the RNAse-H degradation of the pathogenic SOD1 mRNA transcript which reduces levels of the toxic SOD1mutant protein (Miller et al., 2020).”
BackgroundVu, L. T., Garcia‐Mansfield, K., Pompeiano, A., An, J., David‐Dirgo, V., Sharma, R., Venugopal, V., Halait, H., Marcucci, G., Kuo, Y., et al. (2023) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51890 · Cited by 22
“Currently, neurofilament light chain (NfL) 3,4 and phosphorylated neurofilament heavy chain (pNFH) 5 are the most promising biomarkers for ALS and have been used as exploratory outcome measures in ALS clinical trials, 6,7 ª 2023 The Authors.”
MethodAmyotrophic Lateral Sclerosis and Other Motor Neuron Diseases
Izenberg, A. (2023) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001345 · Cited by 22
The Diverse Roles of Reactive Astrocytes in the Pathogenesis of Amyotrophic Lateral Sclerosis
Yang, K., Liu, Y., & Zhang, M. (2024) · Brain Sciences · doi:10.3390/brainsci14020158 · Cited by 29
“The newly approved drug tofersen, an antisense oligonucleotide that reduces SOD1 protein synthesis, holds promise [14].”
BackgroundCurrent potential therapeutics of amyotrophic lateral sclerosis
Lu, L., Deng, Y., & Xu, R. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1402962 · Cited by 26
Crook, A., Jacobs, C., Newton-John, T. R. O., & McEwen, A. (2022) · Journal of Genetic Counseling · doi:10.1002/jgc4.1591 · Cited by 21
Gagliardi, D., Ripellino, P., Meneri, M., Bo, R. D., Antognozzi, S., Comi, G. P., Gobbi, C., Ratti, A., Ticozzi, N., Silani, V., et al. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1169689 · Cited by 22
Nucleic Acid–Based Therapeutics in Orphan Neurological Disorders: Recent Developments
Khorkova, O., Hsiao, J. H., & Wahlestedt, C. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.643681 · Cited by 22
“Lumbar puncture–related adverse events were observed in most participants (Miller et al., 2020).”
BackgroundIncreased chitotriosidase 1 concentration following nusinersen treatment in spinal muscular atrophy
Freigang, M., Steinacker, P., Wurster, C. D., Schreiber‐Katz, O., Osmanovic, A., Petri, S., Koch, J. C., Rostasy, K. M., Falkenburger, B. H., Ludolph, A. C., et al. (2021) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-021-01961-8 · Cited by 22
Self-citationBarker, S. J., Thayer, M. B., Kim, C., Tatarakis, D., Simon, M. J., Dial, R. L., Nilewski, L., Wells, R. C., Zhou, Y., Afetian, M. E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.25.538145 · Cited by 21
“IT oligonucleotide delivery is not without its limitations, including diffusion-mediated biodistribution that results in reduced drug levels in deeper brain regions and increased levels in lumbar spinal cord [12], as well as the potential for adverse events related to IT dosing that can lead to dose level limitations…”
BackgroundWasielewska, J. M., Chaves, J. C. S., Cabral-da-Silva, M. C., Pecoraro, M., Viljoen, S. J., Nguyen, T. H., Bella, V. L., Oikari, L. E., Ooi, L., & White, A. R. (2024) · Fluids and Barriers of the CNS · doi:10.1186/s12987-024-00565-1 · Cited by 22
“ALS is a fatal neurodegenerative condition with approved treatment options being limited to riluzole [72], edara-vone [73] and tofersen antisense oligonucleotide [10, 74] therapies.”
BackgroundLiu, Z., Zhang, H., Lu, K., Chen, L., Zhang, Y., Xu, Z., Zhou, H., Sun, J., Xu, M., Ouyang, Q., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114660 · Cited by 20
Ou, K., Jia, Q., Li, D., Li, S., Li, X., & Yin, P. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00466-9 · Cited by 23
Tofersen and other antisense oligonucleotides in ALS
Ludolph, A., & Wiesenfarth, M. (2025) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864251313915 · Cited by 19
“…concept of ALS as a primary disease of corticoefferent axons as established by Braak et al. 15 In the first phase I–II tofersen trial, 24 it was shown that multiple intrathecal dosing of the drug up to 100 mg induced only minor side effects; most were related to lumbar puncture such…”
Self-citationMansour, H. M., & El-Khatib, A. S. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177529 · Cited by 20
Damme, P. V., Tilkin, P., Mercer, K. J., Terryn, J., D’Hondt, A., Herne, N., Tousseyn, T., Claeys, K. G., Thal, D. R., Zachrisson, O., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa160 · Cited by 21
“It is unclear why CSF VEGF levels at day 85 were lower than those at day 39, although similar drug level reductions have been observed after intrathecal administration of antisense oligonucleotides (Miller et al., 2020).”
BackgroundTime for optimism in amyotrophic lateral sclerosis
Corcia, P., Lunetta, C., Vourc’h, P., Pradat, P., & Blasco, H. (2023) · European Journal of Neurology · doi:10.1111/ene.15738 · Cited by 20
“Gene therapy, pioneered with tofersen in ALS for patients with SOD1 mutation, might be considered one of the major conceptual therapeutic advances in ALS [15].”
BackgroundInfluentialBagyinszky, E., Hulme, J., & An, S. S. A. (2023) · Cells · doi:10.3390/cells12151948 · Cited by 21
Guan, T., Zhou, T., Zhang, X., Guo, Y., Yang, C., Lin, J. J., Zhang, J. V., Cheng, Y., Marzban, H., Wang, Y. T., et al. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04956-9 · Cited by 20
Antisense therapy: a potential breakthrough in the treatment of neurodegenerative diseases
Romanò, R., & Bucci, C. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385285 · Cited by 21
“The phase I/II trial revealed that the highest concentration of the drug is more effective in reducing SOD1 concentration in the CSF compared to lower doses (NCT02623699) but considering the small number of patients enrolled, the trial was expanded to a phase III trial (Miller et al., 2020).”
BackgroundGenomic and transcriptomic advances in amyotrophic lateral sclerosis
Rizzuti, M., Sali, L., Melzi, V., Scarcella, S., Costamagna, G., Ottoboni, L., Quetti, L., Brambilla, L., Papadimitriou, D. A., Verde, F., et al. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102126 · Cited by 23
“Despite its ability to modify the expression of toxic SOD1 protein and decrease plasma NfL, the clinical benefit and long-term effects of this ASO are currently under investigation (Miller et al., 2020, 2022).”
BackgroundMòdol‐Caballero, G., García-Lareu, B., Herrando‐Grabulosa, M., Verdés, S., López‐Vales, R., Pagès, G., Chillón, M., Navarro, X., & Bosch, A. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01025-6 · Cited by 20
Baird, M., Likhite, S. B., Vetter, T. A., Caporale, J. R., Girard, H. B., Roussel, F. S., Howard, A. E., Schwartz, M. K., Reed, A. R., Kaleem, A., et al. (2024) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2024.101312 · Cited by 19
“42,44 A striking hallmark of ALS and other neurodegenerative disorders is neuroin fl ammation, which involves an intricate balance of anti-in-fl ammatory and pro-in fl ammatory mediators.”
Muratet, F., Teyssou, E., Chiot, A., Boillée, S., Lobsiger, C. S., Bohl, D., Gyorgy, B., Guégan, J., Marie, Y., Amador, M. D. M., et al. (2021) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-325921 · Cited by 19
Self-citationKluss, J. H., Lewis, P. A., & Greggio, E. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2082937 · Cited by 19
Park, J. H., Nordström, U., Tsiakas, K., Keskin, I., Elpers, C., Mannil, M., Heller, R., Nolan, M. A., Alburaiky, S., Zetterström, P., et al. (2022) · Brain Communications · doi:10.1093/braincomms/fcad017 · Cited by 18
“Homozygosity for SOD1 c.335dupG, p.C112Wfs*11 is associated with a severe neurological phenotype and elevated plasma neurofilament levels Following the identification of the first two cases exhibiting a severe neurodevelopmental phenotype associated with p.C112X, a call for additional patients was issued through an em…”
InfluentialSelf-citationTsioras, K., Smith, K. C., Edassery, S. L., Garjani, M., Li, Y., Williams, C., McKenna, E. D., Guo, W., Wilen, A. P., Hark, T. J., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113160 · Cited by 21
Witzel, S., Wagner, M., Zhao, C., Kandler, K., Graf, E., Berutti, R., Oexle, K., Brenner, D., Winkelmann, J., & Ludolph, A. C. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.07.005 · Cited by 18
Self-citationFrawley, L., Taylor, N. T., Sivills, O., McPhillamy, E., To, T. D., Wu, Y. T., Chin, B. Y., & Wong, C.-Y. (2024) · Biomedicines · doi:10.3390/biomedicines13010035 · Cited by 18
Gene Therapy for Rare Neurological Disorders
Flotte, T. R., & Gessler, D. J. (2022) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2543 · Cited by 20
“Significantly, the highest dosed patient group demonstrated reduced CSF SOD1, but most patients also experienced lumbar puncture– related adverse effects, which might put additional strain on patients who already must cope with a devastating diagnosis.(52) Around the same time, using a different gene therapy platform,…”
BackgroundToxic SOD1 trimers are off-pathway in the formation of amyloid-like fibrils in ALS
Hnath, B., & Dokholyan, N. V. (2022) · Biophysical Journal · doi:10.1016/j.bpj.2022.04.037 · Cited by 18
A roadmap to ALS prevention: strategies and priorities
Benatar, M. G., Goutman, S. A., Staats, K. A., Feldman, E. L., Weisskopf, M. G., Talbott, E. O., Dave, K. D., Thakur, N. M., & Al‐Chalabi, A. (2023) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2022-330473 · Cited by 18
“8 9 This confluence of factors has facilitated the launch of the first-ever ALS prevention trial (NCT04856982) of a genetic therapy, tofersen, in carriers of highly penetrant SOD1 mutations, which are associated with rapidly progressive ALS.”
BackgroundHale, O. J., Wells, T. R., Mead, R. J., & Cooper, H. J. (2024) · Nature Communications · doi:10.1038/s41467-024-50514-7 · Cited by 20
“Overall,theseresultshaveimplicationsforunderstandingtherole of SOD1 toxic gain of function in ALS, which is particularly relevant in the context of therapeutics which reduce mutant SOD1 levels in ALS patient CNS, such as Tofersen 57,58 .”
Vidovic, M., Lapp, H. S., Weber, C., Plitzko, L., Seifert, M., Steinacker, P., Otto, M., Hermann, A., & Günther, R. (2024) · Brain Communications · doi:10.1093/braincomms/fcae288 · Cited by 16
Disease Mechanisms and Therapeutic Approaches in C9orf72 ALS-FTD
Mayl, K., Shaw, C. E., & Lee, Y. (2021) · Biomedicines · doi:10.3390/biomedicines9060601 · Cited by 18
“Antisense Oligonucleotides The most clinically advanced therapeutic approaches currently involve the use of antisense oligonucleotides (ASOs).”
BackgroundResultInfluentialEsselin, F., Cruz, E. D. L., Hirtz, C., Tiers, L., Alphandery, S., Baudesson, L., Taïeb, G., Camu, W., & Lehmann, S. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13894 · Cited by 17
RNAGenesis: A Generalist Foundation Model for Functional RNA TherapeuticsPreprint
Zhang, Z., Jin, R., Chao, L., Xu, G., Zhang, Y., Zhou, G., Yin, D., Guo, Y., Fu, Y., Yang, Y., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.30.630826 · Cited by 19
Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration
Copley, K. E., Mauna, J. C., Danielson, H. L., Chen, Q., Ozguney, B., Ngo, M., Xie, L., Smirnov, A., Davis, M., Mayne, L., et al. (2026) · Science · doi:10.1126/science.adv3301 · Cited by 16
Kleinerová, J., Chipika, R. H., Tan, E. L., Yunusova, Y., Marchand‐Pauvert, V., Kassubek, J., Pradat, P., & Bede, P. (2025) · Biomedicines · doi:10.3390/biomedicines13030559 · Cited by 19
“The recognition and routine assessment of the sensory system is crucial for precision clinical evaluation, disease monitoring and the understanding of disease biology.”
Tofersen: A Review in Amyotrophic Lateral Sclerosis Associated with SOD1 Mutations
McGuigan, A., & Blair, H. A. (2025) · CNS Drugs · doi:10.1007/s40263-025-01204-5 · Cited by 21
“…p.Leu107Val and p.Val149Gly) and a pre-randomisation Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) score rate of decline of ≥ 0.2 points per month [23], or having another SOD1 mutation and a pre-randomisation ALS-FRS-R score rate of decline of ≥ 0.9 points per month.”
InfluentialNavigating the next frontier in biomedicine: breakthroughs and insights in nucleic acid therapeutics
Wu, S., Zhang, Z., Zhao, Z., Cui, C., & Tan, W. (2026) · Chemical Science · doi:10.1039/d5sc06966a · Cited by 21
“216 The molecule incorporates 2 0 -”
Chisholm, C. G., Lum, J. S., Farrawell, N. E., & Yerbury, J. J. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.335786 · Cited by 16
“An antisense oligonucleotide for SOD1 is currently in phase II clinical trials and has been shown to effectively reduce cerebrospinal fluid SOD1 concentrations (Miller et al., 2020).”
Advanced Gene-Targeting Therapies for Motor Neuron Diseases and Muscular Dystrophies
Chamakioti, M., Karantzelis, N., & Taraviras, S. L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094824 · Cited by 17
“Regarding safety, except for the CSF pleocytosis in some patients for an unknown reason, most adverse events were ascribed to the lumbar puncture procedure [67].”
BackgroundProtein kinetics of superoxide dismutase‐1 in familial and sporadic amyotrophic lateral sclerosis
Ly, C. V., Ireland, M. D., Self, W. K., Bollinger, J., Jockel, J., Herzog, H., Allred, P., Miller, L., Doyle, M., Anez-Bruzual, I., et al. (2023) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51784 · Cited by 15
“16,17 In addition, a strategy involving SOD1 targeting microRNA (miRNA) delivered via adeno-associated virus (AAV) 18 was cleared for Phase I/II trial.”
MethodSelf-citationYan, J., Wang, Y., Hellwig, A., & Bading, H. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101413 · Cited by 16
Profiling tofersen as a treatment of superoxide dismutase 1 amyotrophic lateral sclerosis
Santos, M. O., & de Carvalho, M. A. (2024) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2024.2355983 · Cited by 16
“This SOD1 targeting ASO induces RNase H-mediated degradation of SOD1 mRNA, thus reducing the SOD1 protein synthesis and their toxic intracellular accumulation [24].”
BackgroundInfluentialCrose, J. J., Crose, A., Ransom, J. T., & Lightner, A. L. (2024) · Neurodegenerative Disease Management · doi:10.1080/17582024.2024.2344396 · Cited by 21
Sharma, R., Khan, Z., Mehan, S., Gupta, G. D., & Narula, A. S. (2024) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2024.108518 · Cited by 18
Katô, H., Sato, H., Okuda, M., Wu, J., Koyama, S., Izumi, Y., Waku, T., Iino, M., Aoki, M., Arawaka, S., et al. (2021) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2021.2012699 · Cited by 16
“Tofersen is an antisense oligonucleotide of SOD1 mRNA and inhibits SOD1 protein synthesis (19).”
BackgroundAlarcan, H., Ojaimi, Y. A., Lanznaster, D., Escoffre, J., Corcia, P., Vourc’h, P., Andres, C. R., Veyrat‐Durebex, C., & Blasco, H. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12071071 · Cited by 17
The Beginning of Genomic Therapies for ALS
Hardiman, O. M., & van den Berg, L. H. (2020) · New England Journal of Medicine · doi:10.1056/nejme2012930 · Cited by 16
Bono, N., Fruzzetti, F., Farinazzo, G., Candiani, G., & Marcuzzo, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26125671 · Cited by 20
“…not reach the primary clinical efficacy endpoint at 28 weeks, although subsequent analyses suggested potential benefits with more prolonged treatment, leading to its accelerated approval by the FDA in 2023 [118], with the expectation that clinical benefit would be confirmed in subsequent studies.”
Fahmy, N. A., Müller, K., Andersen, P. M., Marklund, S. L., Otto, M., Ludolph, A. C., & Hamdi, N. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11489-x · Cited by 15
“With the development of SOD1-targeting therapies for ALS patients, currently in clinical trials [2, 3], the discovery of novel SOD1 variants is of high importance.”
BackgroundSelf-citationLibonati, L., Cambieri, C., Colavito, D., Moret, F., D'Andrea, E., Giudice, E. D., Leon, A., Inghilleri, M., & Ceccanti, M. (2023) · Journal of Neurology · doi:10.1007/s00415-023-12142-x · Cited by 17
“Moreover, the recently available antisense oligonucleotide (ASO) therapy for patients with the SOD1 variant [19] and the upcoming similar therapies for C9 orf 72, FUS and ATXN variants [20] highlights the need to identify as many patients as possible with potentially treatable forms of ALS [21].”
Ansari, U., Alam, M., Nadora, D., Muttalib, Z., Chen, V., Taguinod, I., Fitzpatrick, M. J., Wen, J., Ansari, Z., & Lui, F. (2024) · AIMS neuroscience · doi:10.3934/neuroscience.2024010 · Cited by 15
“The most common adverse effects were related to the drug’s lumbar puncture administration and displayed mild to moderate severity, including headache, dizziness, and post-lumbar puncture syndrome [15].”
BackgroundLuan, T., Li, Q., Huang, Z., Feng, Y., Xu, D., Zhou, Y., Hu, Y., & Wang, T. (2024) · Neuroscience Bulletin · doi:10.1007/s12264-024-01267-2 · Cited by 15
“Moreover, Tofersen (BIIB067) is an ASO targeting mRNA, which has an effect on reducing mutant SOD1 [193].”
Getting the Dose Right in Drug Development for Rare Diseases: Barriers and Enablers
AHMED, M. A., Krishna, R., Rayad, N., Albusaysi, S., Mitra, A., Shang, E. Y., Hon, Y. Y., Abuasal, B., Bakhaidar, R. B., Roman, Y. M., et al. (2024) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3407 · Cited by 15
“24 IT delivery, in which drugs are administered directly into the cerebrospinal fluid (CSF) space, enables bypassing the BBB.”
Promise of Nucleic Acid Therapeutics for Amyotrophic Lateral Sclerosis
Ito, D. (2021) · Annals of Neurology · doi:10.1002/ana.26259 · Cited by 15
“in order to suppress the SOD1 level.(26) This drug has to be administered by lumbar puncture and intrathecal infusion every month.”
BackgroundMethylome analysis of ALS patients and presymptomatic mutation carriers in blood cells
Ruf, W. P., Hannon, E. J., Freischmidt, A., Grozdanov, V., Brenner, D., Müller, K., Knehr, A., Günther, K., Dorst, J., Ammerpohl, O., et al. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.04.003 · Cited by 14
Self-citationRomanò, R., Luca, M. D., Fiore, V. S. D., Pecoraro, M., Lattante, S., Sabatelli, M., Bella, V. L., & Bucci, C. (2022) · Brain Communications · doi:10.1093/braincomms/fcac315 · Cited by 15
“The treatment has proved to reduce SOD1 levels in the cerebrospinal fluid, but the study was not designed to test the safety and clinical efficacy of the drug.(62) However, in October 2021, the results of another study were released.”
ResultVandermeulen, L., Geric, I., Fumagalli, L., Kreir, M., Lu, A., Nonneman, A., Premereur, J., Wolfs, L., Policarpo, R., Fattorelli, N., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00725-9 · Cited by 16
“These chemical modifications are now considered the gold standard and are also validated to be safe and tolerated for direct CNS delivery in humans [38, 39, 91, 92].”
BackgroundNusinersen Wearing-Off in Adult 5q-Spinal Muscular Atrophy Patients
Osmanovic, A., Schreiber‐Katz, O., & Petri, S. (2021) · Brain Sciences · doi:10.3390/brainsci11030367 · Cited by 14
“lateral sclerosis (ALS), a drug dose-dependent effect on CSF protein concentration was also reported [29].”
BackgroundTang, L., Dorst, J., Chen, L., Liu, X., Ma, Y., Günther, K., Michels, S., Müller, K., Freischmidt, A., Weishaupt, J. H., et al. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-021-00266-x · Cited by 15
Self-citationTherapeutic Targets in Amyotrophic Lateral Sclerosis: Focus on Ion Channels and Skeletal Muscle
Tarantino, N., Canfora, I., Camerino, G. M., & Pierno, S. (2022) · Cells · doi:10.3390/cells11030415 · Cited by 14
Hamatani, T., Atsuta, N., Sano, F., Nakamura, R., Hayashi, Y., & Sobue, G. (2024) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2024.2309989 · Cited by 13
Amyotrophic lateral sclerosis; clinical features, differential diagnosis and pathology
van Es, M. A. (2024) · International review of neurobiology · doi:10.1016/bs.irn.2024.04.011 · Cited by 15
Vinceti, M., Urbano, T., Filippini, T., Bedin, R., Simonini, C., Sorarú, G., Trojsi, F., Michalke, B., & Mandrioli, J. (2024) · Biological Trace Element Research · doi:10.1007/s12011-024-04311-4 · Cited by 13
Leykam, L., Forsberg, K., Nordström, U., Hjertkvist, K., Öberg, A., Jonsson, E., Andersen, P. M., Marklund, S. L., & Zetterström, P. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106718 · Cited by 14
“A number of drug trials have been performed, first in rodent models and later in symptomatic ALS patients with SOD1 mutations (Borel et al., 2016; Miller et al., 2020; Miller et al., 2022; Miller et al., 2013).”
BackgroundSelf-citationSearching Far and Genome-Wide: The Relevance of Association Studies in Amyotrophic Lateral Sclerosis
Rich, K. A., Roggenbuck, J., & Kolb, S. J. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.603023 · Cited by 14
Lamas, N. J., & Roybon, L. (2021) · Frontiers in Drug Discovery · doi:10.3389/fddsv.2021.773424 · Cited by 12
“Furthermore, only SOD1-ALS patients seem to benefit from SOD1 antisense oligonucleotide therapy, arimoclomol and pyrimethamine (Lange et al., 2017; Benatar et al., 2018; Miller et al., 2020).”
BackgroundContardo, M., Gioia, R. D., Gagliardi, D., Comi, G. P., Ottoboni, L., Nizzardo, M., & Corti, S. P. (2022) · Biomedicines · doi:10.3390/biomedicines10020399 · Cited by 14
“It is in early and late clinical trial development for other neurodegenerative disorders such as amyotrophic lateral sclerosis [42] and Parkinson’s and Alzheimer’s diseases [43].”
BackgroundBrüge, A., Ponimaskin, E. G., & Labus, J. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100071 · Cited by 13
Peters, O. M., & Brown, R. H. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85654-6.00026-5 · Cited by 12
Vazquez-Costa, J. F., Borrego‐Hernández, D., Paradas, C., Gómez‐Caravaca, M. T., Rojas‐García, R., Varona, L., Povedano, M., García‐Sobrino, T., Pascual, I. J., Gutierrez, A. M., et al. (2022) · European Journal of Neurology · doi:10.1111/ene.15661 · Cited by 13
“The description of the phenotype and natural history of each SOD1 mutation is key in a context where tofersen (an antisense oligonucleotide) has shown promising results [11, 12] and might be approved.”
BackgroundDuBord, A. Y., Paolillo, E. W., & Staffaroni, A. M. (2023) · Journal of Diabetes Science and Technology · doi:10.1177/19322968231171399 · Cited by 12
“33,34 Thus, the preclinical phase of neurodegenerative and cerebrovascular disease presents a time-sensitive opportunity for intervention and enrollment in clinical trials, making early detection of cognitive changes in T2D an urgent unmet need.”
BackgroundEconomic evaluation of Motor Neuron Diseases: a nationwide cross-sectional analysis in Germany
Heinrich, F., Cordts, I., Günther, R., Stolte, B., Zeller, D., Schröter, C., Weyen, U., Regensburger, M., Wolf, J., Schneider, I., et al. (2023) · Journal of Neurology · doi:10.1007/s00415-023-11811-1 · Cited by 12
“Estimations of QALYs are rare for ALS and HSP, but can provide important evidence for decision makers regarding upcoming pharmaceutical [13, 39] and non-pharmaceutical therapies of MND.”
BackgroundSelf-citationHarmonized standard operating procedures for administering the ALS functional rating scale-revised
Shefner, J. M., Bunte, T. M., Kittle, G., Genge, A. L., & van den Berg, L. H. (2023) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2023.2260832 · Cited by 12
Self-citationThe Underestimated Relevance of Alzheimer’s Disease Copathology in Amyotrophic Lateral Sclerosis
Barba, L., Otto, M., & Abu‐Rumeileh, S. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230900 · Cited by 11
Witzel, S., Statland, J., Steinacker, P., Otto, M., Dorst, J., Schuster, J., Barohn, R. J., & Ludolph, A. C. (2023) · European Journal of Neurology · doi:10.1111/ene.16154 · Cited by 12
Self-citationAmyotrophic lateral sclerosis: exploring pathophysiology in the context of treatment
Genge, A. L., Wainwright, S., & Velde, C. V. (2023) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2023.2278503 · Cited by 13
Self-citationMajor advances in amyotrophic lateral sclerosis in 2020
Hardiman, O. M. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30447-6 · Cited by 12
Hypoventilation syndrome in neuromuscular disorders
Wenninger, S., & Jones, H. N. (2021) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000973 · Cited by 12
“Tofersen, an antisense oligonucleotide for patients with fALS with SOD1 mutations, showed promising results by slowing disease progression measured by ALSFRS-R score [85].”
MethodHirunagi, T., Sahashi, K., Meilleur, K. G., & Katsuno, M. (2022) · Genes · doi:10.3390/genes13010109 · Cited by 13
“Reliable assays for detecting mutant AR or other biomarkers in serum or CSF are required for clinical trials.”
BackgroundInfluentialAmador, M. D. M., Gargiulo, M., Boucher, C., Herson, A., Staraci, S., Salachas, F., Clot, F., Cazeneuve, C., Ber, I. L., & Dürr, A. (2020) · Neurology Genetics · doi:10.1212/nxg.0000000000000538 · Cited by 12
Self-citationMarlow, T. R., Bowden, K. M., Collins, M. O., & Shaw, P. J. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107124 · Cited by 12
Self-citationRNA therapeutics for neurological diseases
Brentari, I., Zadorozhna, M., Denti, M. A., & Giorgio, E. (2023) · British Medical Bulletin · doi:10.1093/bmb/ldad010 · Cited by 11
Vanderhaeghe, S., Prerad, J., Tharkeshwar, A. K., Goethals, E., Vints, K., Beckers, J., Scheveneels, W., Debroux, E., Princen, K., Damme, P. V., et al. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01866-0 · Cited by 13
“A notable exception is the recently discovered antisense oligonucleotide tofersen, which slows down disease progression in ALS patients carrying mutations in SOD1 [26, 27].”
BackgroundSimple In-Cell Processing Enables Deep Proteome Analysis of Low-Input Caenorhabditis elegans
Elsayyid, M. W., Tanis, J. E., & Yu, Y. (2025) · Analytical Chemistry · doi:10.1021/acs.analchem.4c05003 · Cited by 13
de Souza, P. V. S., Pinto, W. B. V. D. R., Farias, I. B., Badia, B. D. M. L., Pinto, I. F. N., Costa, G. C., Marin, C. M., Jorge, A. C. D. S., Souto, E. C., Serrano, P. D. L., et al. (2021) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-021-01993-0 · Cited by 11
“Since 1993, when SOD1 gene variants were first associated to familial ALS, more than 150 variants have been described and the mechanism of SOD1 protein dysfunction in the pathophysiology of disease was partially elucidate, and new genetic therapies are emerging from recent clinical trials and are on the verge of being…”
BackgroundGarcia, D. A., Powers, A. F., Bell, T. A., Guo, S., & Aghajan, M. (2021) · Nucleic Acid Therapeutics · doi:10.1089/nat.2021.0029 · Cited by 11
Martinelli, I., Ghezzi, A., Zucchi, E., Gianferrari, G., Ferri, L., Moglia, C., Manera, U., Solero, L., Vasta, R., Canosa, A., et al. (2023) · Journal of Neurology · doi:10.1007/s00415-023-11963-0 · Cited by 11
“Accordingly, an antisense oligonucleotide targeting SOD1 has been developed [11, 12] and is currently being administered through an early access program in many countries (NCT04972487) and has recently gained FDA approval.”
BackgroundHoward, J., Bekker, H., McDermott, C. J., & McNeill, A. (2024) · Journal of Medical Genetics · doi:10.1136/jmg-2023-109735 · Cited by 11
Self-citationAdvances in gene therapy for neurogenetic diseases: a brief review
Xie, Y., Lv, W., Chen, Y., Hong, S., Yao, X., Chen, W., & Zhao, M. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02167-y · Cited by 11
“In 2020, a phase I/II clinical trial with 50 patients revealed lower SOD1 concentration in the cerebrospinal fluid in the tofersen group compared with the placebo group after intrathecal administration over 12 weeks [17].”
BackgroundAn age‐dependent mathematical model of neurofilament trafficking in healthy conditions
Paris, A., Bora, P., Parolo, S., Monine, M. I., Tong, X., Eraly, S. A., Masson, E., Ferguson, T. A., McCampbell, A., Graham, D. L., et al. (2022) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12770 · Cited by 11
Self-citationOjaimi, Y. A., Dangoumau, A., Alarcan, H., Hergesheimer, R. C., Vourc’h, P., Corcia, P., Lanznaster, D., & Blasco, H. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2083958 · Cited by 11
“For instance, one of the most widely used ALS animal models is the transgenic mutant SOD1 model.”
BackgroundInfluentialFrequency of C9orf72 and SOD1 mutations in 302 sporadic ALS patients from three German ALS centers
Yilmaz, R., Grehl, T., Eckrich, L., Marschalkowski, I., Weishaupt, K., Valkadinov, I., Simic, M., Brenner, D., Andersen, P. M., Wolf, J., et al. (2023) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2023.2165946 · Cited by 10
“In phase I/II studies, the highest dose of tofersen led to reduced SOD1 and neurofilament levels in cerebrospinal fluid (12).”
BackgroundSelf-citationIranian clinical practice guideline for amyotrophic lateral sclerosis
Boostani, R., Olfati, N., Shamshiri, H., Salimi, Z., Fatehi, F., Hedjazi, S. A., Fakharian, A., Ghasemi, M., Okhovat, A. A., Basiri, K., et al. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1154579 · Cited by 12
Heishima, K., Aketa, N., Heishima, M., & Kawachi, A. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1250766 · Cited by 13
Tryptophan residues in TDP-43 and SOD1 modulate the cross-seeding and toxicity of SOD1
Pokrishevsky, E., DuVal, M. G., McAlary, L., Louadi, S., Pozzi, S., Roman, A. Y., Plotkin, S. S., Dijkstra, A. A., Julien, J., Allison, W. T., et al. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107207 · Cited by 12
Quigley, S., Quigg, K. H., & Goutman, S. A. (2025) · CNS Drugs · doi:10.1007/s40263-025-01217-0 · Cited by 10
Metadata
- Authors
- Miller, T., Cudkowicz, M., Shaw, P. J., Andersen, P. M., Atassi, N., Bucelli, R. C., Genge, A., Glass, J., Ladha, S., Ludolph, A. L., Maragakis, N. J., McDermott, C. J., Pestronk, A., Ravits, J., Salachas, F., Trudell, R., Van Damme, P., Zinman, L., Bennett, C. F., Lane, R., Sandrock, A., Runz, H., Graham, D., Houshyar, H., McCampbell, A., Nestorov, I., Chang, I., McNeill, M., Fanning, L., Fradette, S., & Ferguson, T. A.
- Affiliations
- From the Washington University School of Medicine, St. Louis (T.M., R.C.B., A.P.); the Healey Center for ALS, Massachusetts General Hospital, Harvard Medical School, Boston (M.C., N.A.), and Biogen, Cambridge (A.S., H.R., D.G., H.H., A.M., I.N., I.C., L.F., S.F., T.A.F.) — both in Massachusetts; the Sheffield Institute for Translational Neuroscience, University of Sheffield, and NIHR Sheffield Biomedical Research Centre and Clinical Research Facility, University of Sheffield and Sheffield Teaching...
- Harvard University (US)
- Montreal Neurological Institute and Hospital (CA)
- Barrow Neurological Institute (US)
- Biogen (United States) (US)
- ORCID
- Cudkowicz, Merit
- Shaw, Pamela J.
- Andersen, Peter M.
- Atassi, Nazem
- Bucelli, Robert C.
- Genge, Angela
- Glass, Jonathan
- Ladha, Shafeeq
- Maragakis, Nicholas J.
- McDermott, Christopher J.
- Pestronk, Alan
- Ravits, John
- Trudell, Randall
- Zinman, Lorne
- Bennett, C. Frank
- Lane, Roger
- Runz, Heiko
- Graham, Danielle
- McCampbell, Alexander
- Nestorov, Ivan
- Chang, Ih
- Fradette, Stephanie
- Ferguson, Toby A.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-07-09
- Volume
- 383
- Issue
- 2
- Pages
- 109-119
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3040840440
- Cited by
- 565
- References
- 27
- Citations by year
- 2026: 64 · 2025: 73 · 2024: 87 · 2023: 90 · 2022: 130 · 2021: 83 · 2020: 36
- FWCI
- 36.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Funders
- National Institute for Health and Care Research (NF-SI-0617-10077)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Keywords
- tofersen, antisense oligonucleotides, amyotrophic lateral sclerosis, SOD1, intrathecal administration, pleocytosis, dose escalation
- MeSH terms
- Superoxide Dismutase-1, Adult, Amyotrophic Lateral Sclerosis, Dose-Response Relationship, Drug, Double-Blind Method, Female, Headache, Humans, Injections, Spinal, Intermediate Filaments, Leukocytosis, Male, Middle Aged, Mutation, Oligonucleotides, Vital Capacity, Oligonucleotides, Antisense, Disease Progression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
