Quantification of video-oculography as a biomarker for remyelination – An example from fampridine in internuclear ophthalmoplegia

Abstract

A recent study showed that video-oculography was sensitive to the effect of fampridine on ocular movement speed and amplitude in internuclear ophthalmoplegia (INO), resulting from improved nerve transduction (Kanhai et al. 2019, doi: https://doi.org/10.1111/cns.13096). This can be used as a biomarker of remyelination for the investigation of new therapeutic compounds in multiple sclerosis (MS). We aimed to quantify the acute effect of fampridine on peak velocity versional dysconjugacy index (PV-VDI) and first peak amplitude (FPA-VDI) of eye movements. Population modelling was used to quantify FPA-VDI and PV-VDI for each eye in 23 patients with INO (10 unilateral, 13 bilateral), aged 31–72 yo. Correlations between eyes were taken into account, and fampridine potency and maximum efficacy were estimated according to a sigmoidal relationship. Fampridine effect on PV-VDI and FPA-VDI in each eye was accurately described and predicted (Fig. 1). Fampridine could maximally improve PV-VDI and FPA-VDI by 32.8% and 30.7% respectively, with 8.43 mg/L the concentration at which 50% of efficacy was reached. Repetitive testing worsened scores by around 0.8% for each additional test. Strong correlation was found for baseline PV-VDI and FPA-VDI between each other and between occasions. All parameters were estimated with good precision (RSE <30%). Baseline characteristics and fampridine effect were quantified for the new remyelination biomarker of video-oculography. Model-based drug development allows more efficient clinical trials using optimal design and clinical trial simulation exercises (Milligan et al. 2013, doi:https://doi.org/10.1038/clpt.2013.54), our model enables this for the investigation of new compounds in diseases involving demyelination.