Marmoset (a small size NHP): Incorporation of safety pharmacology endpoints in toxicology studies

The common marmoset (Callithrix jacchus) is a nonhuman primate species that is already used in biomedical research. Due to the constrained supply of Cynomolgus monkey and the acute shortage of sexually mature animals arisen during the COVID-19 Pandemic, the marmoset has been increasingly used for toxicity testing of biotherapeutic proteins. However, incorporating safety pharmacology endpoints in marmoset toxicology studies was not as optimal as in Cynomolgus. Therefore, the purpose of this study was to test a jacketed telemetry system (DECRO system) which enables the simultaneous recordings of respiratory, ECG and activity parameters in freely moving marmosets. Ten animals (5 females and 5 males) were fitted with the Decro system and recorded for 14 h. Respiratory rate (RespR), expiratory and inspiratory times, tidal volume, minute ventilation, ECG analysis and intervals calculation, heart rate (HR), and activity level (AL) were assessed in all animals. During the light phase, the mean values ± SEM of HR and RespR varied from 271 ± 12 beat per min (bpm) to 318 ± 14 bpm, and from 63 ± 3 breath per min (brpm) to 73 ± 2 brpm, respectively based on the AL. During the dark cycle where AL was nearly null, the HR and RespR decreased to 247 ± 12 bpm and 53 ± 4 bpm, respectively. All the remaining parameters were successfully assessed using the different algorithms provided by the software. Overall, our results provided evidence that there were no clinical findings caused by the jacket. This preliminary study yielded promising results to support the use of the GLP software version of this jacketed telemetry system, in line with the 3Rs principles, in regulatory toxicology studies. With this development, the use of marmosets as an alternative to Cynomolgus in drug development is reinforced especially if considering that marmosets are one of the very few species capable of showing drug-induced torsades de pointes in healthy animals.