Assessment of Neurofilament Light Protein as a Serum Biomarker in Rodent Models of Toxic-Induced Peripheral Neuropathy

Abstract

Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a side effect frequently caused by common antitumor drugs, which may induce a severe and persistent limitation of the quality of life of cancer patients. Today, nerve conduction studies are considered the most objective indicators for CIPN diagnosis. Unfortunately, they are not easily available at most oncology centers. Therefore, a noninvasive and highly sensitive method is required to confirm nerve damage. Increased evidence supports the potential utility of fluid-based biomarkers to predict tissue damage and to monitor neurotoxicity due to drug administration or the efficacy of disease-modifying treatments. Neurofilaments, the major intermediate filaments in neurons that are specifically expressed in axons, have been investigated as potential biomarker candidates that might be used for this purpose. Neurofilament light chain (NfL) protein is increasingly proposed as a blood biomarker in several neurological diseases mainly affecting the central nervous system. In addition, analysis of serum NfL was evaluated also in peripheral neuropathies including Guillain–Barré syndrome, chronic inflammatory demyelinating and vasculitic neuropathies, and Charcot–Marie–Tooth. This chapter aims to provide an overview of the methods that allow NfL quantification in serum, focusing on the most recent ultrasensitive single molecule array (Simoa) assay. This technique is likely to be the best method for NfL dosage in CIPN models to predict the onset of large caliber neuronal dysfunction. Since blood sampling is an easily accessible technique, serum NfL may provide important help to monitor neuroaxonal damage after chemotherapy treatment, and might represent promising tools to follow CIPN progress.