B10 Further development of the minipig tongue-test using quantitative motor measurements

Abstract

Background Large animal models, such as the transgenic (tg) Huntington disease (HD) minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in minipigs to establish similar endpoints in preclinical and clinical studies. The tongue protrusion assessment (glossomotography) was successfully established as part of the Q-Motor system and showed correlated to UHDRS-TMS motor dysfunction and changes in brain imaging in premanifest and manifest HD. Recently, a tongue test was also established to assess minipig motor performance. Aim The aim of this project was to further develop the minipig tongue test to incorporate quantitative measurements. The tgHD minipigs do not show any overt changes in their behavior, thus sensitive assessment of minor changes detectable compared to wildtype (wt) minipigs would be useful. Methods The existing tongue board has been modified to use it with only one hole. At the bottom of the hole a force sensor was mounted connected to an Arduino Uno R3 to readout the sensor and a Raspberry Pi 3B to log the recorded data. To be able to expose animals to variable degrees of motor challenge, the hole depths was adjustable in depth. To motivate the minipigs to touch the sensor with their tongue the hole was filled with soaked feed pellets as reward. Results The tongue protrusion force was measured in three different levels of depths. Reliable and well reproducible assessment was feasible, but were no differences between wt and tgHD minipigs were detected at the age investigated. Conclusion The developed tongue board is able to measure quantitative tongue protrusion forces. The next step is to explore whether minipigs can be trained to actively press their tongue against the sensor to obtain a pre-defined reward. Acknowledgement This study was funded by donations of HD families.