Quantification of gait in mitochondrial m.3243A > G patients: a validation study

Abstract

BackgroundMore than half of the patients harbouring the m.3243A > G mutation were found to have trouble maintaining balance when walking in a recent study by our group. Others demonstrated that these patients had an abnormal gait pattern, as quantified by gait analysis. Gait analysis is an emerging method to quantify subtle changes in walking pattern, also during therapeutic interventions. Therefore, we aimed to test the reliability and reproducibility of gait analysis and select the most suitable protocol for this group of patients using a GAITRite electronic walkway. Four different protocols were tested: normal walking, dual task, post exercise and after a ten minutes of rest.ResultsIn total 36 patients with the m.3243A > G mutation and 50 healthy controls were enrolled in this study. Overall high intra class correlation coefficients were found in all experimental conditions for both patients and healthy controls indicating good reproducibility. Marked differences in gait between patients and controls were observed and were in line with the only available exploratory study performed. There was a good correlation between both the overall NMDAS score, NMDAS subscale scores, both markers for disease severity, and specific gait parameters.ConclusionsThe observed reliability of the test makes GAITRite a suitable instrument for intervention studies in patients with mitochondrial disease.

The KHENERGY Study: Safety and Efficacy of KH176 in Mitochondrial m.3243A>G Spectrum Disorders

“…In recent studies, more than half of the patients harboring the m.3243A>G mutation were found to have trouble maintaining balance when walking. Others demonstrated that these patients had an abnormal gait pattern, as quantified by gait analysis . For this reason, and the observation that gait improved during KH176 treatment in a mitochondrial disease mouse model, gait was chosen as a primary end point .…”

“…[19][20][21][22] For this reason, and the observation that gait improved during KH176 treatment in a mitochondrial disease mouse model, gait was chosen as a primary end point. 17,19,20 This 28-day phase IIA study showed no improvement in gait parameters. This can be explained by the fact that 16 of 18 patients participating in this study already had a normal gait at baseline.…”

Erratum to: Quantification of gait in mitochondrial m.3243A > G patients: a validation study

“…Upon publication of this article [ 1 ] it was noticed that Table 2 was incorrect. During Production, errors were introduced into the Variable column.…”

Feeding difficulties, a key feature of the Drosophila NDUFS4 mitochondrial disease model

“…The need for relevant animal models that recapitulate the symptoms of a disease is crucial to understand and elucidate the pathomechanisms, and to later use the models to develop therapeutic strategies. Feeding difficulties have frequently been reported in patients with CI deficiencies ( van den Engel-Hoek et al, 2017 ; Kisler et al, 2010 ; Koene et al, 2012 , 2013 ; de Laat et al, 2015 ; Morava et al, 2006 ; Ramakers et al, 2017 ; Read et al, 2012 ; Smeitink, 2003 ), but have largely been neglected in animal models for mitochondrial disease. Here, we present a novel Drosophila model of CI deficiency which develops a dramatic feeding impairment, along with other symptoms recapitulating CI-deficient NDUFS4-mutated patient characteristics, such as a severely reduced lifespan, locomotor defects and signs of neurodegeneration.…”