Serum neurofilament levels correlate with electrodiagnostic evidence of axonal loss in paclitaxel-induced peripheral neurotoxicity

Velasco, Roser; Marco, Carla; Mariotto, Sara; Stradella, Agostina; Hernández, J.; Pernas, Sònia; Ferrari, Sérgio; Bruna, Jordi

doi:10.1007/s00415-022-11377-4

Cited by 12 publications

(17 citation statements)

References 28 publications

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“…93 A secondary analysis of the latter study showed that NfL levels proportionally increase during chemotherapy administration and significantly correlate with NCS sensory abnormalities. 96 Subsequently, elevated NfL from the initial paclitaxel treatment cycle was found to be predictive of CIPN outcomes in 190 ovarian cancer patients. 94 A single study has examined NfL in 34 oxaliplatin treated patients, 97 with elevated NfL occurring following 3 and 6 months of treatment.…”

Section: Emerging Biomarker Evidence Of Axonal Degenerationmentioning

confidence: 99%

Axonal degeneration in chemotherapy-induced peripheral neurotoxicity: clinical and experimental evidence

Park

Cetinkaya-Fisgin²,

Argyriou

et al. 2023

J Neurol Neurosurg Psychiatry

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Multiple pathological mechanisms are involved in the development of chemotherapy-induced peripheral neurotoxicity (CIPN). Recent work has provided insights into the molecular mechanisms underlying chemotherapy-induced axonal degeneration. This review integrates evidence from preclinical and clinical work on the onset, progression and outcome of axonal degeneration in CIPN. We review likely triggers of axonal degeneration in CIPN and highlight evidence of molecular pathways involved in axonal degeneration and their relevance to CIPN, including SARM1-mediated axon degeneration pathway. We identify potential clinical markers of axonal dysfunction to provide early identification of toxicity as well as present potential treatment strategies to intervene in axonal degeneration pathways. A greater understanding of axonal degeneration processes in CIPN will provide important information regarding the development and progression of axonal dysfunction more broadly and will hopefully assist in the development of successful interventions for CIPN and other neurodegenerative disorders.

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Section: Emerging Biomarker Evidence Of Axonal Degenerationmentioning

confidence: 99%

Axonal degeneration in chemotherapy-induced peripheral neurotoxicity: clinical and experimental evidence

Park

Cetinkaya-Fisgin²,

Argyriou

et al. 2023

J Neurol Neurosurg Psychiatry

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“…113,115 NfL is also a good marker of severity with serum levels rising in proportion to the degree of axonal damage (demonstrated by nerve conduction studies) in paclitaxel-treated patients. 116 These findings, describing comparable preclinical and clinical pathological testing for CIPN, have potential to improve early recognition. It is important to recognise that results are often nuanced, and considerable follow-up work is required before robust reliability in both settings is established.…”

Section: Pathological Assessments With Preclinical and Clinical Relev...mentioning

confidence: 68%

“…Furthermore, NfL is a potentially sensitive clinical marker, 111 with studies demonstrating significant elevation in serum prior to the development of CIPN in patients treated with both paclitaxel and carboplatin, highlighting its potential predicative value 113,115 . NfL is also a good marker of severity with serum levels rising in proportion to the degree of axonal damage (demonstrated by nerve conduction studies) in paclitaxel‐treated patients 116 …”

Section: Pathological Assessment Of Cipn Using Preclinical Modelsmentioning

confidence: 98%

Targeting translation: A review of preclinical animal models in the development of treatments for chemotherapy‐induced peripheral neuropathy

White

Abdulla

Park

et al. 2023

J Peripheral Nervous Sys

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Background and Aims The expanding use of chemotherapy in curative cancer treatment has simultaneously resulted in a substantial and growing cohort of cancer survivors with prolonged disability from chemotherapy‐induced peripheral neuropathy (CIPN). CIPN is associated with several commonly prescribed chemotherapeutics, including taxanes, platinum‐based drugs, vinca alkaloids, bortezomib and thalidomide. These distinct classes of chemotherapeutics, with their varied neurotoxic mechanisms, often cause patients to suffer from a broad profile of neuropathic symptoms including chronic numbness, paraesthesia, loss of proprioception or vibration sensation and neuropathic pain. Decades of investigation by numerous research groups have provided substantial insights describing this disease. Despite these advances, there is currently no effective curative or preventative treatment option for CIPN and only the dual serotonin–norepinephrine reuptake inhibitor Duloxetine is recommended by clinical guidelines for the symptomatic treatment of painful CIPN. Methods In this review, we examine current preclinical models, with our analysis focused on translational relevance and value. Results Animal models have been pivotal in achieving a better understanding of the pathogenesis of CIPN. However, it has been challenging for researchers to develop appropriate preclinical models that are effective vehicles for the discovery of translatable treatment options. Interpretation Further development of preclinical models targeting translational relevance will promote value for preclinical outcomes in CIPN studies.

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“…[165][166][167] For example, serum neurofilament concentrations are increased in animal models and cancer patients with chemotherapy-induced peripheral neuropathy (CIPN). [168][169][170][171] Blood and CSF levels of NfL have been demonstrated to be a useful indicator of sensory neuron injury in DRG of asymptomatic rodents (Fader et al 172 and unpublished data) and NHPs 9,172 following a single AAV-based GTx administration, and these levels correlated well with the severity of microscopic changes in DRG and nerves up to 12 months post-injection. 9,172 Several factors, such as biofluid kinetics, clearance, and degradation as well as the use of immunosuppressive therapies, stage of disease and/or injury, 173,174 variations related to lifestyle, age, 175 and procedure-related/handling effects 176 can affect circulating NfL values.…”

Section: Correlation Between Functional and Structural Findings In Se...mentioning

confidence: 91%

Scientific and Regulatory Policy Committee Points to Consider: Sampling, Processing, Evaluation, Interpretation, and Reporting of Test Article-Related Ganglion Pathology for Nonclinical Toxicity Studies

Bennet,

Pardo,

Assaf

et al. 2023

Toxicol Pathol

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Certain biopharmaceutical products consistently affect dorsal root ganglia, trigeminal ganglia, and/or autonomic ganglia. Product classes targeting ganglia include antineoplastic chemotherapeutics, adeno-associated virus-based gene therapies, antisense oligonucleotides, and anti-nerve growth factor agents. This article outlines “points to consider” for sample collection, processing, evaluation, interpretation, and reporting of ganglion findings; these points are consistent with published best practices for peripheral nervous system evaluation in nonclinical toxicity studies. Ganglion findings often occur as a combination of neuronal injury (e.g., degeneration, necrosis, and/or loss) and/or glial effects (e.g., increased satellite glial cell cellularity) with leukocyte accumulation (e.g., mononuclear cell infiltration or inflammation). Nerve fiber degeneration and/or glial reactions may be seen in nerves, dorsal spinal nerve roots, spinal cord, and occasionally brainstem. Interpretation of test article (TA)-associated effects may be confounded by incidental background changes or experimental procedure-related changes and limited historical control data. Reports should describe findings at these sites, any TA relationship, and the criteria used for assigning severity grades. Contextualizing adversity of ganglia findings can require a weight-of-evidence approach because morphologic changes of variable severity occur in ganglia but often are not accompanied by observable overt in-life functional alterations detectable by conventional behavioral and neurological testing techniques.

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Serum neurofilament levels correlate with electrodiagnostic evidence of axonal loss in paclitaxel-induced peripheral neurotoxicity

Cited by 12 publications

References 28 publications

Axonal degeneration in chemotherapy-induced peripheral neurotoxicity: clinical and experimental evidence

Axonal degeneration in chemotherapy-induced peripheral neurotoxicity: clinical and experimental evidence

Targeting translation: A review of preclinical animal models in the development of treatments for chemotherapy‐induced peripheral neuropathy

Scientific and Regulatory Policy Committee Points to Consider: Sampling, Processing, Evaluation, Interpretation, and Reporting of Test Article-Related Ganglion Pathology for Nonclinical Toxicity Studies

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