Historical control data of nonclinical nerve conduction parameters in nonhuman primates

Abstract

Damage to the peripheral nervous system (neuropathy) can develop as a side effect of certain classes of therapeutic compounds or from toxin exposure, disease, and traumatic injury. Given the clinical significance of neuropathy, it can be critical to characterize nerve function during the nonclinical safety assessment of certain classes of compounds. Additionally, recent characterization of dorsal root ganglion toxicity following adeno-associated viral therapies stresses the need for in vivo assessment of potential nerve damage on these studies. Nerve conduction evaluations provide an electrophysiological approach to assess nerve function, are a sensitive and valid index of induced neuropathies, can be conducted at multiple time points throughout the treatment period, and provide quantitative data for evaluation. Here, we present a dataset of normative values for nerve conduction parameters in nonhuman primates generated by a retrospective analysis of historical control data from 16 Charles River studies comprising 491 young adult male and female cynomolgus monkeys, approximately 1.5–5 years of age. Nerve panels consisted of distal hindlimb peroneal motor and sural sensory nerves, a proximal mixed segment of the hindlimb sciatic nerve, and distal forelimb median sensory nerve. Evaluation parameters included response onset latency, nerve conduction velocity (NCV), and amplitude, as appropriate, for each nerve with animal sex and country of origin as independent variables. NCV values for each nerve were largely consistent between studies while response amplitudes exhibited more variability, indicating the importance of establishing prestudy baselines and incorporating a concurrent control group for postdose assessments. No sex differences were observed for NCV or amplitude parameters, indicating that sexes can be pooled to increase sample size and experimental power while potentially reducing the total animals required for each study. An animal country of origin effect on response parameters was observed which related, in part, to differences in animal size. Collectively, the dataset provides a comprehensive overview of control values for young adult cynomolgus monkeys to assess the sensitivity of the technique to properly characterize a potential effect. It is considered suitable to aid in the interpretation of potential neuropathy for nerve conduction evaluations used in nonclinical toxicology studies.