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 301–400 of 565
Entering the era of precision medicine to treat amyotrophic lateral sclerosis
Theunissen, F., Flynn, L. L., Iacoangeli, A., Khleifat, A. A., Al‐Chalabi, A., Giordano, J. J., Strømme, M., & Akkari, P. A. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00890-5 · Cited by 12
“…dose study of tofersen reported reduc‑ tion of SOD1 protein in cerebrospinal fluid (CSF) for all dose groups, and was accompanied with a decline in clinical measures of ALS for highest dose group (100 mg), particularly in patients with variants associated with fast progression of the disease [16].”
New antisense oligonucleotide therapies reach first base in ALS
Lopez, E. R., Borschel, W. F., & Traynor, B. J. (2022) · Nature Medicine · doi:10.1038/s41591-021-01629-7 · Cited by 10
Catasús, N., Rosas, I., Bonache, S., Negro, A., Torres‐Martín, M., Plana‐Pla, A., Salvador, H., Serra, E., Blanco, I., & Castellanos, E. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.10.026 · Cited by 10
STING-Induced Inflammation — A Novel Therapeutic Target in ALS?
Damme, P. V., & Robberecht, W. (2021) · New England Journal of Medicine · doi:10.1056/nejmcibr2031048 · Cited by 10
Iyer, A. K., Schoch, K. M., Verbeck, A. C., Galasso, G., Chen, H., Smith, S. E., Oldenborg, A., Miller, T. M., Karch, C. M. M., & Bonni, A. (2023) · PLoS ONE · doi:10.1371/journal.pone.0294731 · Cited by 9
Self-citationKouhi, Z. H., Seyedalipour, B., Hosseinkhani, S., & Chaichi, M. J. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.136701 · Cited by 11
Amador, M. D. M., Muratet, F., Teyssou, E., Boillée, S., & Millecamps, S. (2021) · Revue Neurologique · doi:10.1016/j.neurol.2021.01.008 · Cited by 9
Imbimbo, B. P., Triaca, V., Imbimbo, C., & Nisticò, R. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.363185 · Cited by 9
“tofersen in 50 patients with ALS due to SOD1 mutations, the highest drug dose of 100 mg given intrathecally over a period of 12 weeks decreased significantly, compared to baseline, CSF SOD1 levels by 33% (Miller et al., 2020).”
BackgroundÇakar, A., Pekbilir, E., Ceylaner, S., Durmuş, H., Battaloğlu, E., Şahin, U., & Parman, Y. (2023) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2023.2189925 · Cited by 9
“Accordingly, emerging targeted therapies aim to silence the SOD1 gene (9).”
BackgroundDučić, T., & Koch, J. C. (2023) · Cells · doi:10.3390/cells12111451 · Cited by 9
“, tofersen [20]), were shown to have some effect on disease progression, but so far no therapy has been able to stop or even cure ALS.”
BackgroundNeurologic orphan diseases: Emerging innovations and role for genetic treatments
Kioutchoukova, I. P., Foster, D. T., Thakkar, R. N., Foreman, M. A., Burgess, B. J., Toms, R., Valero, E., & Lucke-Wold, B. P. (2023) · World Journal of Experimental Medicine · doi:10.5493/wjem.v13.i4.59 · Cited by 11
Advancing mechanistic understanding and biomarker development in amyotrophic lateral sclerosis
Thompson, A. G., Oeckl, P., Feneberg, E., Bowser, R. P., Otto, M., Fischer, R., Kessler, B. M., & Turner, M. R. (2021) · Expert Review of Proteomics · doi:10.1080/14789450.2021.2004890 · Cited by 9
“Antisense oligonucleotide therapies targeting the common gene mutations in ALS have reached the clinical trial arena in symptomatic patients [94].”
BackgroundKessler, C., Serna-Higuita, L. M., Wilke, C., Rattay, T. W., Hengel, H., Reichbauer, J., Stransky, E., Leyva, A., Mengel, D., Synofzik, M., et al. (2022) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51518 · Cited by 9
“Levels of cNfL decreased in a clinical trial of Tofersen in ALS while not correlating with clinical measures; therefore, cNfL levels indicated a therapy response without being a monitoring biomarker over the length of the trial.(50) Thus, the use of sNfL as a therapy-response biomarker in SPG4 needs to be examined in…”
The Advent of Omics Sciences in Clinical Trials of Motor Neuron Diseases
Ruffo, P., Cavallaro, S., & Conforti, F. L. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12050758 · Cited by 9
“Since this drug, approved as a diabetes mellitus remedy, demonstrated beneficial effects through different signalling pathways [28], the trial aim was to evaluate CSF deregulated Repeat-associated non-AUG (RAN) protein levels.”
InfluentialTreatment of hereditary amyotrophic lateral sclerosis
Corcia, P., Blasco, H., Beltran, S., Piegay, A., & Vourc’h, P. (2022) · Revue Neurologique · doi:10.1016/j.neurol.2022.09.001 · Cited by 9
Machacek, M. E., Gogakos, T., Fletcher, M. C., Lunderville, K. A., Swoboda, K. J., & Sohani, A. R. (2020) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.13392 · Cited by 9
Protein kinase inhibitors as therapeutics in neurodegenerative and psychiatric disorders
Tridente, G., Jana, A., Nath, A., & Ashraf, G. M. (2023) · Receptor Tyrosine Kinases in Neurodegenerative and Psychiatric Disorders · doi:10.1016/b978-0-443-18677-6.00015-4 · Cited by 8
Alo, B., & Lamers, C. (2025) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.5c00153 · Cited by 10
CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models
Khan, H., Riaz, H., Ahmed, A., Kiyani, M. M., Jawad, S. M., Shah, S. S. U. D., Abualait, T., Al‐Hussain, F., Li, H., & Bashir, S. (2025) · Regenerative Therapy · doi:10.1016/j.reth.2025.07.009 · Cited by 10
“Trials of ASOs to SOD1 (e.g., tofersen) and C9orf72 expansions have been successful in ALS patients by lowering levels of toxic mRNA/protein [119].”
Antisense oligonucleotide therapy in amyotrophic lateral sclerosis
Erdi-Krausz, G., & Shaw, P. J. (2025) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001413 · Cited by 9
Self-citationFranklin, J., Azzouz, M., & Shaw, P. J. (2020) · Expert Opinion on Orphan Drugs · doi:10.1080/21678707.2020.1835638 · Cited by 8
Self-citationZhu, J., Liu, C., Wang, D., Cao, X., Wang, S., Liu, Y., Wang, J., Li, P., & He, Q. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.706011 · Cited by 8
RNA-Based Therapies for Neurodegenerative Diseases.
Ayala, Y. M., & Nguyen, A. D. (2021) · PubMed Central · Cited by 8
Kumar, M. S., Fowler, M., Kulick, D., Boopathy, S., Gadd, D. H., Rotunno, M., Douthwright, C. L., Golebiowski, D., Yusuf, I. O., Xu, Z., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416013 · Cited by 8
“To overcome the toxicity of ALS-linked SOD1, gene-silencing of SOD1 via microRNAs [12] and antisense oligonucleotides (ASOs) [13,14] has been proposed.”
BackgroundLiao, Y., Cai, H., Luo, F., Li, D., Li, H., Liao, G., Duan, J., Xu, R., & Zhang, X. (2023) · BMC Medical Genomics · doi:10.1186/s12920-023-01441-x · Cited by 8
Prado, M. B., Pedro, K. M., & Adiao, K. J. (2023) · Revue Neurologique · doi:10.1016/j.neurol.2023.01.731 · Cited by 8
Vidovic, M., Menschikowski, M., Freigang, M., Lapp, H. S., & Günther, R. (2024) · Neurological Research and Practice · doi:10.1186/s42466-023-00305-0 · Cited by 8
“The ASO tofersen was developed for patients with superoxide dismutase 1 (SOD1) mutation -associated ALS ( SOD1-ALS) to reduce the toxic SOD1 protein level [3, 4].”
BackgroundResultRicci, C., Giannini, F., Riolo, G., Bocci, S., Casali, S., & Battistini, S. (2021) · Genes · doi:10.3390/genes12101544 · Cited by 8
“This disease progression may be similar to that reported for the p.A5V or p.A5T [26,30], however without involvement of bulbar muscles.”
BackgroundInfluentialCrook, A., Jacobs, C., Newton-John, T. R. O., & McEwen, A. (2022) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2022.2051553 · Cited by 8
“In addition to providing the opportunity for certain patients to be involved in emerging genotype-targeted therapy trials (9), detection of a pathogenic variant provides relatives with the option to clarify their risk through predictive/presymptomatic genetic testing or to inform future family planning decisions throu…”
BackgroundOligonucleotides: A novel area of interest for drug delivery in neurodegenerative diseases
Alharbi, K. S., Shaikh, M. A. J., Afzal, O., Altamimi, A. S. A., Almalki, W. H., Kazmi, I. A., Al-Abbasi, F. A., Alzarea, S. I., Babu, M. R., Singh, S. K., et al. (2022) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2022.103849 · Cited by 8
Significance of gene therapy in neurodegenerative diseases
Wang, L., Ma, L., Gao, Z., Wang, Y., & Qiu, J. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1515255 · Cited by 7
“ASOs targeting SOD1 (ASOs-SOD1) are designed to reduce SOD1 expression, which holds promise for slowing the progression of ALS and prolonging patient survival during clinical treatment (Miller et al., 2020).”
Chemical Modifications in Nucleic Acid Therapeutics
Lennox, K. A., Young, R. C., & Behlke, M. A. (2025) · Methods in molecular biology · doi:10.1007/978-1-0716-4742-4_3 · Cited by 8
Targeting Protein Aggregation in ALS
Perni, M., & Mannini, B. (2024) · Biomolecules · doi:10.3390/biom14101324 · Cited by 8
“By day 85, mutant SOD1 protein levels in cerebrospinal fluid (CSF) decreased by 3% in the low-dose group and 36% in the high-dose group compared to the placebo [41].”
BackgroundWismayer, M. F., Wismayer, A. F., Pace, A., Vassallo, N., & Cauchi, R. J. (2021) · European Journal of Human Genetics · doi:10.1038/s41431-021-00975-x · Cited by 7
Therapeutic Approaches to Amyotrophic Lateral Sclerosis from the Lab to the Clinic
Chavda, V. P., Patel, C. A., Modh, D. H., Ertaş, Y. N., Sonak, S. S., Munshi, N. K., Anand, K., Soni, A., & Pande, S. V. (2022) · Current Drug Metabolism · doi:10.2174/1389200223666220310113110 · Cited by 8
Ding, Y., Botchway, B. O. A., Zhang, Y., Jin, T., & Liu, X. (2022) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2022.151921 · Cited by 8
Clinical gene therapy development for the central nervous system: Candidates and challenges for AAVs
Leong, T. W., Pal, A., Cai, Q., Gao, Z., Li, X., Bleris, L. G., Hayenga, H. N., & Qin, Z. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.04.009 · Cited by 7
Nanocrystalline gold (CNM-Au8): a novel bioenergetic treatment for ALS
Vucic, S., & Kiernan, M. C. (2023) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2023.2263368 · Cited by 7
“Overall, these disease-modifying therapies exhibit marginal efficacy and survival benefit with effectiveness evident in a select cohort of patients [3–7].”
BackgroundSite-blocking antisense oligonucleotides as a mechanism to fine-tune MeCP2 expression
Vanderplow, A. M., Dodis, G. E., Rhee, Y., Cikowski, J., Gonzalez, S., Smith, M. L., & Gogliotti, R. G. (2024) · RNA · doi:10.1261/rna.080220.124 · Cited by 6
The parasagittal dural space of the human brain
Donahue, M. J., McKnight, C. D., Claassen, D. O., & Hett, K. (2025) · Brain · doi:10.1093/brain/awaf204 · Cited by 6
“57,58 Although these trials have been unsuccessful to date, 56,59 it is not unreasonable that pene-trance of the agents themselves might be increased, relative to intravenous injection, and penetrance could be increased further as our knowledge of CSF flow topography and contributions to…”
Astrocytes Contribute to Motor Neuron Degeneration in ALS via the TRAIL ‐ DR5 Signaling Pathway
Yang, K., Liu, Y., Deng, W., Gong, Z., Huang, L., Li, Z., & Zhang, M. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70146 · Cited by 6
“Current treatment options are limited and largely ineffective, which may be attributed to the unclear etiology and pathogenesis of ALS (Aschenbrenner 2023; Brooks et al. 2022; Fels et al. 2022; Jaiswal 2019; Miller et al. 2020; Paganoni et al. 2020).”
Guo, J., Zou, Q., Xu, J., Lei, J., Yin, X., Li, B., Fu, J., Mi, J., Wang, Y., Huang, H., et al. (2025) · Brain · doi:10.1093/brain/awaf291 · Cited by 6
“14 However, RNAi therapies face several challenges in clinical applications.”
Verdés, S., Navarro, X., & Bosch, A. (2025) · Human Gene Therapy · doi:10.1177/10430342251372898 · Cited by 8
Oligonucleotide–siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial
Chen, W., Jiang, L., Duan, C., Kang, M., Ye, J., Wang, L., Pan, Y., Qu, H., Liao, X., Zhou, X., et al. (2026) · Nature Medicine · doi:10.1038/s41591-026-04491-7 · Cited by 6
“Direct comparisons should be cautious given substantial differences—the cited tofersen trials enriched faster-progressing variants, while many variants in this study have slower natural history progression 12,33,34 .”
Clinical studies in amyotrophic lateral sclerosis
Dorst, J., & Genge, A. L. (2022) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001099 · Cited by 7
Self-citationPromising approaches to the pathogenetic therapy of amyotrophic lateral sclerosis
Kutlubaev, M. A. (2024) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202412404113 · Cited by 6
Current neuroprotective therapies and future prospects for motor neuron disease
Evans, L. J., O’Brien, D., & Shaw, P. J. (2024) · International review of neurobiology · doi:10.1016/bs.irn.2024.04.003 · Cited by 5
Self-citationGuerra, S., Chung, R. S., Yerbury, J. J., & Karl, T. (2021) · Genes Brain & Behavior · doi:10.1111/gbb.12735 · Cited by 6
Peters, S., Wirkert, E., Kuespert, S., Heydn, R., Johannesen, S. W., Friedrich, A., Mailänder, S., Korte, S., Mecklenburg, L., Aigner, L., et al. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14010200 · Cited by 6
“The pathophysiology is complex and heterogeneous, but collectively, ALS leads to premature degeneration of motor neurons in the motor cortex and spinal cord (upper and lower motor neurons) in all patients [11,12].”
BackgroundInfluentialRespiratory onset of amyotrophic lateral sclerosis in a pregnant woman with a novel SOD1 mutation
Masrori, P., Ospitalieri, S., Forsberg, K., Moens, T. G., Poesen, K., Race, V., Brännström, T., Andersen, P. M., Thal, D. R., & Damme, P. V. (2022) · European Journal of Neurology · doi:10.1111/ene.15224 · Cited by 6
“Both intrathecal infusion of antisense oligonucleotides, and adenoassociated virus delivering antiSOD1 microRNA are presently being evaluated in clinical trials [6,7].”
BackgroundSelf-citationInclusions in macrophages of the cerebrospinal fluid during treatment with Tofersen
Sparasci, D., Castelli, C., Staedler, C., Gobbi, C., & Ripellino, P. (2022) · Muscle & Nerve · doi:10.1002/mus.27763 · Cited by 7
“Only one case of clinically relevant myelitis has been observed following tofersen administration.(3) However, little is known about possible changes in CSF cytology during treatment with tofersen.”
BackgroundInfluentialGenetic-Based Treatment Strategies for Muscular Dystrophy and Congenital Myopathies
Findlay, A. R., & Weihl, C. C. (2022) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001203 · Cited by 6
Sharma, R. K. (2023) · Current Gene Therapy · doi:10.2174/1566523223666230911120922 · Cited by 6
Targeting low levels of MIF expression as a potential therapeutic strategy for ALS
Alfahel, L., Gschwendtberger, T., Kozareva, V., Dumas, L., Gibbs, R., Kertser, A., Baruch, K., Zaccai, S., Kahn, J., Thau‐Habermann, N., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101546 · Cited by 6
Short structural variants as informative genetic markers for ALS disease risk and progression
Theunissen, F., Flynn, L. L., Anderton, R. S., & Akkari, P. A. (2022) · BMC Medicine · doi:10.1186/s12916-021-02206-y · Cited by 6
“Additionally, this SSV may also help to identify patients that could benefit from a SOD1 targeted therapy, such as the SOD1 suppressing antisense therapy Tofersen (currently in phase III extension study) [43].”
BackgroundInfluentialIguchi, N., Mano, T., Iwasa, N., Ozaki, M., Yamada, N., Kikutsuji, N., Kido, A., & Sugie, K. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.853469 · Cited by 6
“The time from the allocation day to an event needs to take into account the effects of other factors such as the patient’s stage of inclusion and living environment (45).”
BackgroundVemula, P., Schoch, K. M., & Miller, T. M. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1320182 · Cited by 5
Self-citationA neuromuscular clinician’s primer on machine learning
Yeo, C. J. J., Ramasamy, S., Leong, F.-L., Nag, S., & Simmons, Z. (2025) · Journal of Neuromuscular Diseases · doi:10.1177/22143602251329240 · Cited by 5
“83,84 In one study, unsupervised ML was used to identify ALS subtypes in deeply-phenotyped, population-based collections of patients from Italy, then supervised ML was used to build predictor models that could accurately classify individual patients.”
Antisense oligonucleotide therapies for monogenic disorders
Krey, I., Ferro, I., & Wagner, M. (2025) · Medizinische Genetik · doi:10.1515/medgen-2025-2025 · Cited by 6
Lépine, S., Maussion, G., Schneider, A., Nauleau-Javaudin, A., Castellanos‐Montiel, M. J., Ambriz, G. J., Spiegelman, D., Abdian, N., Franco-Flores, A. K., Haghi, G., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-12147-8 · Cited by 6
“At present, the few available treatments (i.e., riluzole 3–5 , edaravone 6,7 ) offer modest benefits or are only efficacious in a subset of patients, as is the case for the SOD1-lowering therapy tofersen 8–10 .”
Mini review: Gene therapy targets for aging-associated diseases
Shchukina, E., Eremin, I. I., Mazunin, I., & Alexey, M. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152708 · Cited by 5
Challenges and opportunities in nanotherapeutics targeted for central nervous system disorders
Yong, J. M., Hakobyan, K., Mahmud, S. A. Z., Johnson, D., Lee, J., Diwan, A. D., Gu, Z., Moalem‐Taylor, G., & Mao, G. (2025) · Nanoscale · doi:10.1039/d5nr02463c · Cited by 5
Cook, B. E., McLaren, D. G., Sullivan, J. M., Fakhri, G. E., Yokell, D. L., Freeman, M. W., Currier, N. V., Oestergaard, M. E., Dobson, H., Hesterman, J. Y., et al. (2025) · Journal of Nuclear Medicine · doi:10.2967/jnumed.125.270731 · Cited by 6
Self-citationStable isotope labelling kinetics of neurofilament light
Leckey, C. A., Giovannucci, T. A., Coulton, J. B., He, Y., Sato, C., Ghoshal, N., Vignarajah, T., Jaunmuktane, Z., Barthélemy, N. R., Zetterberg, H., et al. (2025) · Brain Communications · doi:10.1093/braincomms/fcaf468 · Cited by 6
Genç, B., Nho, B., Seung, H., Helmold, B., Park, H., Gözütok, Ö., Kim, S. H., Park, J., Ye, S., Lee, H., et al. (2023) · Gene Therapy · doi:10.1038/s41434-023-00383-4 · Cited by 6
Ethics of gene and cell therapy development for neurologic disorders
Kimmelman, J. (2024) · Handbook of clinical neurology · doi:10.1016/b978-0-323-90120-8.00002-2 · Cited by 5
Atterton, C., Trew, I., Cale, J. M., Aung-Htut, M. T., Grens, K., Kiernan, J., Delagrammatikas, C. G., & Piper, M. (2025) · Disease Models & Mechanisms · doi:10.1242/dmm.052300 · Cited by 7
Barriers to Tofersen Therapy for Variant SOD1 -Mediated ALS
Appel, S. H., & Thonhoff, J. R. (2024) · JAMA Neurology · doi:10.1001/jamaneurol.2024.3331 · Cited by 5
Incremental Gains in the Battle against ALS
Benatar, M. G., & McDermott, M. (2020) · New England Journal of Medicine · doi:10.1056/nejme2021144 · Cited by 5
A bibliometric analysis of gene editing and amyotrophic lateral sclerosis (from 2004 to 2024)
Wan, H., Qian, W., Wei, B., Tian, K., Chen, Z., Zhang, J., & Chen, F. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1499025 · Cited by 4
PEG-ASO conjugates for efficient targeted delivery and migration inhibition in Cancer cell
Zhao, C., Li, X., He, Z., Ye, C., Chen, F., & Cheng, J. R. (2025) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2025.130208 · Cited by 4
Kang, D. M., Lukianenko, N., Baik, J., Kim, Y. K., & Lim, S. (2025) · ChemBioChem · doi:10.1002/cbic.202500316 · Cited by 4
Nair, A. P., Tejwani, S., Dinakaran, S., Shetty, N., Shetty, R., Ghosh, A., & Sethu, S. (2025) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.66.13.24 · Cited by 5
Furlan, R., Sapio, A. D., Ferraro, D., Rossi, E., Valentino, P., & Terracciano, D. (2026) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2025-1743 · Cited by 4
“…by its role as a pharmacodynamic biomarker in the development of the antisense oligonucleotide tofersen for SOD1-related familial ALS: despite the failure to meet the primary clinical endpoint, regulatory approval was supported by biomarker evidence demonstrating reductions in NfL levels [22].”
Transport pathways across the blood-brain barrier for waste clearance and drug delivery
Gröbner, L. S., & Pietrzik, C. U. (2026) · Fluids and Barriers of the CNS · doi:10.1186/s12987-026-00812-7 · Cited by 4
“Through lumbar puncture, ASOs enter the CSF and were shown to target the SOD1 gene for ALS or tau biomarkers in AD [296, 297].”
Wu, J., Yan, S., Bian, Y., Liu, R., Lyu, X., Zhang, Z., Huang, S., Chen, T., & Cheng, L. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70133 · Cited by 4
“In adults with SOD1-ALS, intrathecal injection of the highest concentration of tofersen (100 mg) for 12 weeks led to a decrease in mutant SOD1 concentration in cerebrospinal fluid (CSF) by inducing RNase-H mediated degradation of mutant SOD1 mRNA (Miller et al. 2020).”
CMC and regulatory aspects of oligonucleotide therapeutics
Rupp, T. M., & Cramer, H. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821595-1.00012-9 · Cited by 4
Waller, R., Bury, J. J., Appleby‐Mallinder, C., Wyles, M., Loxley, G., Babel, A., Shekari, S., Kazoka, M., Wollff, H., Al‐Chalabi, A., et al. (2023) · Brain Communications · doi:10.1093/braincomms/fcad331 · Cited by 4
Self-citationTranslating the ALS Genetic Revolution into Therapies: A Review
Meadows, C., Rau, N. A., Faridi, W., & Ly, C. V. (2024) · Current Treatment Options in Neurology · doi:10.1007/s11940-024-00781-y · Cited by 4
The role of glial cells in amyotrophic lateral sclerosis
Pandya, V. A., & Patani, R. (2024) · International review of neurobiology · doi:10.1016/bs.irn.2024.04.005 · Cited by 5
Du, X., Dong, Q.-X., Zhu, J., Li, L., Yu, X., & Liu, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910392 · Cited by 4
Ando, M., Higuchi, Y., Yuan, J., Yoshimura, A., Yano, C., Hobara, T., Kojima, F., Hiramatsu, Y., Nozuma, S., Nakamura, T., et al. (2025) · Journal of Neurology · doi:10.1007/s00415-025-12925-4 · Cited by 4
“Tofersen, an antisense oligonucleotide, reduces SOD1 expression by promoting the ribonuclease (RNase)- mediated degradation of SOD1 mRNA (messenger RNA), showing significant effects on ALS biomarkers [11, 12].”
Personalized Therapy of Neurological Disorders
Jain, K. K. (2020) · Springer eBooks · doi:10.1007/978-3-030-62080-6_11 · Cited by 4
Gálvez-Llompart, M., Zanni, R., García‐Domenech, R., & Gálvez, J. (2022) · Pharmaceuticals · doi:10.3390/ph15010094 · Cited by 4
“All the molecules on the market to date and the recent molecules selected as potential ALS treatments—see, for example, Tofersen [13]—have been tested against SOD-1, showing controversial results.”
BackgroundNucleic Acid-Based Strategies to Treat Neurodegenerative Diseases
Panda, S., Chatterjee, O., & Chatterjee, S. (2023) · Springer eBooks · doi:10.1007/978-981-19-8520-1_4 · Cited by 4
Motor Neuron Disease Population-Based Registry in Egypt: Where Do We Stand?
Hamdi, N., Ocab, O., Soliman, R., Ludolph, A. C., Anwar, W. A., Logroscino, G., & Fahmy, N. A. (2024) · Neuroepidemiology · doi:10.1159/000539468 · Cited by 4
Self-citationA chemogenomic approach is required for effective treatment of amyotrophic lateral sclerosis
Pampalakis, G., Angelis, G., Zingkou, E., Vekrellis, K., & Sotiropoulou, G. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.657 · Cited by 4
“30 When administered at the onset of symptoms, it does not have any effect on lifespan or motor function of Tg-SOD1G93A, Tg-TDP43A315T and Tg-FUS(1-359) mouse models.”
BackgroundInfluentialApplied Bayesian Approaches for Research in Motor Neuron Disease
Temp, A. G. M., Naumann, M., Hermann, A., & Glaß, H. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.796777 · Cited by 4
“Comparing our Figures 1, 2 of (32), we see that the re-creation was successful as our progression mirrors the original data’s.”
MethodResultInfluentialHermann, P., Koch, J. C., & Zerr, I. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1839048 · Cited by 4
Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis
Swash, M., & de Carvalho, M. A. (2025) · Brain Sciences · doi:10.3390/brainsci15060601 · Cited by 4
“This may require first clearing the cytosol of aberrant, misfolded, and ubiquitinated TDP-43—for example, by antisense nucleotide therapies [43].”
Arreola-Aldape, C. A., Moran-Guerrero, J. A., Monnier, G. P., Flores-Salcido, R. E., Martínez-Ledesma, E., Ruiz‐Manriquez, L. M., Razo-Alvarez, K. R., Mares-Custodio, D., Avalos-Montes, P. J., Figueroa-Sanchez, J. A., et al. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1598336 · Cited by 5
Reza, S., Handique, J., Sharma, P., Mathew, S., Bari, S., Tyagi, N., Sharma, C., Panda, S., Chowdhury, D., Laskar, S., et al. (2025) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2025.2574681 · Cited by 3
“Clinically, the predominance of SOD1 mutations has immediate relevance given the recent approval of tofersen, an antisense oligonucleotide therapy targeting SOD1-ALS (21).”
Raoufinia, R., Alyari, G., Nia, A. T., Abbaszadegan, M. R., Mahmoudi, A., Shafaeibajestan, S., Saburi, E., Tavakol‐Afshari, J., Hassani, M., Jamali, F., et al. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04781-w · Cited by 4
“This reduction in SOD1 protein levels was maintained throughout the 12-week treatment period [173].”
Friec, J. L., Mourier, H., Couly, S., Cubedo, N., Dubois, K., Meunier, J., Delprat, B., de Zordo‐Banliat, A., Ayad, T., Virieux, D., et al. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00527-z · Cited by 3
“…approved by both the US Food and Drug Administration and the European Medicines Agency: Riluzole which prolongs life by only a few months with limited effects on motor deficits [6] and Tofersen, an anti-sense oligonucleotide only dedicated to the 1%–2% of ALS cases with mutations in SOD1 [7, 8].”
Zhao, X., Zheng, Y., Cai, X. T., Yao, Y., & Qin, D. (2026) · Pharmaceuticals · doi:10.3390/ph19010092 · Cited by 5
“The SOD1-directed antisense oligonucleotide (ASO) tofersen, administered intrathecally in SOD1-associated ALS (SOD1-ALS), reduced CSF SOD1 by ~30–40% in the highest-dose cohorts of a phase 1/2 trial and lowered plasma neurofilament light chain (NfL) [173].”
Treating SOD1-ALS with tofersen results in nonprogressive chronic ALS—a case series from Iceland
Thorarinsson, B. L., Sveinsson, O. A., Hilmarsson, A., Sigurþórsdóttir, Þ. B., & Andersen, P. M. (2026) · Journal of Neurology · doi:10.1007/s00415-025-13579-y · Cited by 4
“Clinically meaningful differences in muscle strength and pulmonary function were observed after 52 weeks between the early and delayed treatment groups [6].”
Self-citationObika, S., & Blesa, J. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70445 · Cited by 3
Clinical Trial Development in Frontotemporal Lobar Degeneration
Ljubenkov, P. A., & Boxer, A. L. (2022) · Cambridge University Press eBooks · doi:10.1017/9781108975759.019 · Cited by 3
A Neglected Gene: The Role of the ANG Gene in the Pathogenesis of Amyotrophic Lateral Sclerosis
Zhang, Y., Li, Y., Bin, S., Cheng, X., & Niu, Q. (2024) · Aging and Disease · doi:10.14336/ad.2024.0107 · Cited by 4
Animal Models of FUS-Proteinopathy: A Systematic Review
Rezvykh, A. P., Shteinberg, D. A., Bronovitsky, E. V., Ustyugov, A. A., & Funikov, S. Y. (2024) · Biochemistry (Moscow) · doi:10.1134/s0006297924140037 · Cited by 3
“…therapeutic approaches to ALS are based on autologous stem cell transplantation [168] and antisense oligonucleotides [169, 170] aimed at down-regulating expression of the SOD1 [171], C9orf72 [172], FUS [173], and ATXN2 genes [174] in the patients with verified underlying causes and forms of ALS.”
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
