ArticleMolecular therapy. Methods & clinical development2022
Circulating neurofilament light chain as a promising biomarker of AAV-induced dorsal root ganglia toxicity in nonclinical toxicology species.
Article in Molecular therapy. Methods & clinical development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- Antisense oligonucleotide treatment following viral delivery of artificial SOD1-targeting miRNA shows improved efficacy in SOD1-G93A mice.Molecular therapy. Advances · 2026Article
- Challenging the more-is-better dogma: A precision-optimized AAV gene therapy for SMA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Skeletal Muscle Biomarkers of Amyotrophic Lateral Sclerosis: A Large-Scale, Multi-Cohort Proteomic Study.Annals of neurology · 2026Article
- Intrathalamic delivery of adeno-associated viral vector expressing progranulin as gene therapy for GRN-related frontotemporal dementia.Molecular therapy. Methods & clinical development · 2025Article
- An AAV-Based Therapy Approach for Neurological Phenotypes of X-Linked Adrenoleukodystrophy.International journal of molecular sciences · 2025Review
- Longitudinal evaluation of serum neurofilament light levels in normal healthy volunteers: defining a threshold of concern.Journal of neurology · 2025Article
- AAV-RNAi constructs promote DRG toxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Dorsal root ganglion toxicity after AAV intra-CSF delivery of a RNAi expression construct into non-human primates and mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Adeno-associated virus vectors and neurotoxicity-lessons from preclinical and human studies.Gene therapy · 2025Review
- Comparative assessment of the transduction efficiency and safety associated with the delivery of AAV9-GFP vector via lumbar puncture to cynomolgus macaques with and without anti-AAV9 pre-existing antibodies.Molecular therapy. Methods & clinical development · 2024Article
- Cis-regulatory elements driving motor neuron-selective viral payload expression within the mammalian spinal cord.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- Biomarker Qualification for Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: Theory and Practice.Annals of neurology · 2024Review
- AAV Immunotoxicity: Implications in Anti-HBV Gene Therapy.Microorganisms · 2023Review
- Efficacy and safety of a SOD1-targeting artificial miRNA delivered by AAV9 in mice are impacted by miRNA scaffold selection.Molecular therapy. Nucleic acids · 2023Article
- Identifying the dataset to define the optimal timing of histopathological examination for central nervous system toxicity in MPTP-induced Parkinson's disease monkey model.Journal of toxicologic pathology · 2023Article
- Plasma neurofilament light chain as a potential biomarker of neurodegeneration in murine brain.Toxicology research · 2023Article
- Comparative analysis of neurofilament light chain levels in the serum and cerebrospinal fluid in rats subjected to partial sciatic nerve ligation.Journal of toxicologic pathology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adeno-associated virus (AAV)-induced dorsal root ganglia (DRG) toxicity has been observed in several nonclinical species, where lesions are characterized by neuronal degeneration/necrosis, nerve fiber degeneration, and mononuclear cell infiltration. As AAV vectors become an increasingly common platform for novel therapeutics, non-invasive biomarkers are needed to better characterize and manage the risk of DRG neurotoxicity in both nonclinical and clinical studies. Based on biological relevance, reagent availability, antibody cross-reactivity, DRG protein expression, and assay performance, neurofilament light chain (NF-L) emerged as a promising biomarker candidate. Dose- and time-dependent changes in NF-L were evaluated in male Wistar Han rats and cynomolgus monkeys following intravenous or intrathecal AAV injection, respectively. NF-L profiles were then compared against microscopic DRG lesions on day 29 post-dosing. In animals exhibiting DRG toxicity, plasma/serum NF-L was strongly associated with the severity of neuronal degeneration/necrosis and nerve fiber degeneration, with elevations beginning as early as day 8 in rats (≥5 × 10
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