ReviewThe Lancet. Neurology2025
Amyotrophic lateral sclerosis caused by hexanucleotide repeat expansions in C9orf72: from genetics to therapeutics.
Review in The Lancet. Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Non-Invasive Brain Stimulation for Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Current potential biomarkers for Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis: review of literature.Dialogues in clinical neuroscience · 2026Review
- Insights into X-linked Dystonia-Parkinsonism and Spinocerebellar Ataxia type 36 Through the Lens of Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.Molecular neurobiology · 2026Review
- Convergent TBK1 loss of function drives gasdermin E dependent pyroptosis and motor neuron degeneration across ALS genotypes.Cell death and differentiation · 2026Article
- When copper turns killer: Decoding copper dyshomeostasis and cuproptosis in neurodegenerative pathogenesis and precision metal interventions.Neural regeneration research · 2026Article
- The Impact of Sponsored Genetic Testing in 170 Consecutive Consenting Patients With Amyotrophic Lateral Sclerosis: A Single-Site Retrospective Review.Muscle & nerve · 2026Article
- Regenerative strategies for ALS: stem cells and extracellular vesicles.Discover nano · 2026Review
- Genetic variants among patients with motor neuron disease in Lithuania - a retrospective single-center study.Neurogenetics · 2026Article
- Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS).International journal of molecular sciences · 2026Review
- FUS-associated ALS in Taiwan: genetic spectrum, clinical features, and a founder haplotype of p.H517D.Journal of neurology · 2026Article
- Genetic epidemiology of C9orf72 repeat expansion associated amyotrophic lateral sclerosis in Hungary.Molecular medicine (Cambridge, Mass.) · 2026Article
- CCAAT/enhancer-binding protein delta regulates miRs-4257 and 3156 to attenuate the interleukin 12 through small extracellular vesicle transmission in glioblastoma.Cancer cell international · 2026Article
- Wild-typemedRxiv : the preprint server for health sciences · 2026Article
- Clinical trajectories and genetic profiles of SOD1-related amyotrophic lateral sclerosis: insights from a single-center cohort in India.Journal of neurology · 2026Article
- MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.Molecular neurobiology · 2026Review
- Modeling ALS in a dish: how organoids are transforming research.Frontiers in medicine · 2026Review
- First Korean Case ofJournal of clinical neurology (Seoul, Korea) · 2026Article
- Article
- Axonal transport impairment as an upstream mechanism in amyotrophic lateral sclerosis pathogenesis.Frontiers in neuroscience · 2026Article
- Loss of C9orf72 impacts the peripheral neuromuscular system via immune dysregulation and accelerates the progression of amyotrophic lateral sclerosis in SOD-1 mutant mice.Journal of neuroinflammation · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
GGGGCC repeat expansions in C9orf72 are a common genetic cause of amyotrophic lateral sclerosis in people of European ancestry; however, substantial variability in the penetrance of the mutation, age at disease onset, and clinical presentation can complicate diagnosis and prognosis. The repeat expansion is bidirectionally transcribed in the sense and antisense directions into repetitive RNAs and translated into dipeptide repeat proteins, and both accumulate in the cortex, cerebellum, and the spinal cord. Furthermore, neuropathological aggregates of phosphorylated TDP-43 are observed in motor cortex and other cortical regions, and in the spinal cord of patients at autopsy. C9orf72 repeat expansions can also cause frontotemporal dementia. The GGGGCC repeat induces a complex interplay of loss-of-function and gain-of-function pathological mechanisms. Clinical trials using antisense oligonucleotides to target the GGGGCC repeat RNA have not been successful, potentially because they only target a single gain-of-function mechanism. Novel therapeutic approaches targeting the DNA repeat expansion, multiple repeat-derived RNA species, or downstream targets of TDP-43 dysfunction are, however, on the horizon, together with the development of diagnostic and prognostic biomarkers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.