Preclinical nerve conduction: Nerve battery options for primate studies

Electrophysiological neurodiagnostic tests of nerve conduction (NC) are key assays included in preclinical safety and toxicology programs to assess the peripheral neuropathy (PN) liability of a new drug. Despite their increased use, standardization of nerve conduction studies (NCS) is lacking in the preclinical space, with limited regulatory guidelines stipulating type and number of nerves or minimum combinations appropriate for each stage of drug development or indication. Detection of subtle peripheral toxicities depends on choosing appropriate nerve targets for testing, especially when functional changes remain above the lower limit of normal values. To support robust preclinical toxicology study designs, the current short communication provides options and recommendations for selecting peripheral nerves for clinically translatable nerve conduction batteries applicable to toxicology and gene therapy, with a focus on primate models. A comprehensive compilation of accessible nerve locations is offered including lower and upper extremity motor nerves, and sensory nerves with origin at multiple DRG levels. Rankings of technique difficulty and repeatability across serial collections are presented for each assay informed by serial nerve conduction from 500 adult primates. The goal of this communication is to support the standardization and preclinical implementation of this important assay.