Academic Journal
Therapeutic effects of the mitochondrial ROS-redox modulator KH176 in a mammalian model of Leigh Disease
| العنوان: | Therapeutic effects of the mitochondrial ROS-redox modulator KH176 in a mammalian model of Leigh Disease |
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| المؤلفون: | Haas, R. de, Das, D., Garanto, A., Renkema, G.H., Greupink, R., Broek, P.H.H. van den, Pertijs, J.C., Collin, R.W.J., Willems, P.H., Beyrath, J.D., Heerschap, A., Russel, F.G., Smeitink, J.A.M. |
| المصدر: | Scientific Reports, 7 |
| سنة النشر: | 2017 |
| المجموعة: | Radboud University: DSpace |
| مصطلحات موضوعية: | Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences, Radboudumc 12: Sensory disorders DCMN: Donders Center for Medical Neuroscience, Radboudumc 15: Urological cancers RIMLS: Radboud Institute for Molecular Life Sciences, Radboudumc 16: Vascular damage RIHS: Radboud Institute for Health Sciences, Radboudumc 6: Metabolic Disorders RIMLS: Radboud Institute for Molecular Life Sciences |
| الوصف: | Contains fulltext : 176945.pdf (publisher's version ) (Open Access) ; Leigh Disease is a progressive neurometabolic disorder for which a clinical effective treatment is currently still lacking. Here, we report on the therapeutic efficacy of KH176, a new chemical entity derivative of Trolox, in Ndufs4 -/- mice, a mammalian model for Leigh Disease. Using in vivo brain diffusion tensor imaging, we show a loss of brain microstructural coherence in Ndufs4 -/- mice in the cerebral cortex, external capsule and cerebral peduncle. These findings are in line with the white matter diffusivity changes described in mitochondrial disease patients. Long-term KH176 treatment retained brain microstructural coherence in the external capsule in Ndufs4 -/- mice and normalized the increased lipid peroxidation in this area and the cerebral cortex. Furthermore, KH176 treatment was able to significantly improve rotarod and gait performance and reduced the degeneration of retinal ganglion cells in Ndufs4 -/- mice. These in vivo findings show that further development of KH176 as a potential treatment for mitochondrial disorders is worthwhile to pursue. Clinical trial studies to explore the potency, safety and efficacy of KH176 are ongoing. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://repository.ubn.ru.nl//bitstream/handle/2066/176945/176945.pdf; http://hdl.handle.net/2066/176945; http://dx.doi.org/10.1038/s41598-017-09417-5 |
| DOI: | 10.1038/s41598-017-09417-5 |
| الاتاحة: | http://hdl.handle.net/2066/176945 https://repository.ubn.ru.nl//bitstream/handle/2066/176945/176945.pdf https://doi.org/10.1038/s41598-017-09417-5 |
| رقم الانضمام: | edsbas.A2CBF8A4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-017-09417-5 |
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