Takeshi Kouga1, Mariko Takagi2, Akihiko Miyauchi3, Hiroko Shimbo2, Mizue Iai2, Sumimasa Yamashita2, Kei Murayama4, Matthew B Klein5, Guy Miller5, Tomohide Goto2, Hitoshi Osaka6. 1. Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan; Department of Pediatrics, Jichi Medical University, Tochigi, Japan. 2. Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan. 3. Department of Pediatrics, Jichi Medical University, Tochigi, Japan. 4. Department of Metabolism, Chiba Children's Hospital, Chiba, Japan. 5. BioElectron Technology Corporation, Mountain View, CA, USA. 6. Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan; Department of Pediatrics, Jichi Medical University, Tochigi, Japan. Electronic address: hosaka@jichi.ac.jp.
Abstract
BACKGROUND: Leigh syndrome is a mitochondrial disease caused by respiratory chain deficiency, and there are no proven effective therapies. EPI-743 is a potent cellular oxidative stress protectant and results of clinical trials for mitochondrial diseases are accumulating. CASE: At 5months, a girl presented with the scarce eye movement and diminished muscle tone. She was diagnosed with Leigh encephalopathy from blood and cerebrospinal fluid lactate elevation and MRI findings. Sequence analysis for mitochondrial DNA revealed a T10158C mutation in the mitochondrial encoded ND3 gene in complex I. RESULTS: At 8months, succinate was prescribed expected to restore the electron transport chain system. After that her condition got worse and succinate was discontinued. Subsequent administration of EPI-743 improved her eye movement, fine motor movements of the extremities, and bowel movement. She is now 5years old. Although brain atrophy has progressed, she has still respiratory free time. CONCLUSION: Our patient showed visible improvement with EPI-743 treatment and the only patient surviving after 4years. There is a possibility that EPI-743 is modifying the natural course of the syndrome.
BACKGROUND:Leigh syndrome is a mitochondrial disease caused by respiratory chain deficiency, and there are no proven effective therapies. EPI-743 is a potent cellular oxidative stress protectant and results of clinical trials for mitochondrial diseases are accumulating. CASE: At 5months, a girl presented with the scarce eye movement and diminished muscle tone. She was diagnosed with Leigh encephalopathy from blood and cerebrospinal fluid lactate elevation and MRI findings. Sequence analysis for mitochondrial DNA revealed a T10158C mutation in the mitochondrial encoded ND3 gene in complex I. RESULTS: At 8months, succinate was prescribed expected to restore the electron transport chain system. After that her condition got worse and succinate was discontinued. Subsequent administration of EPI-743 improved her eye movement, fine motor movements of the extremities, and bowel movement. She is now 5years old. Although brain atrophy has progressed, she has still respiratory free time. CONCLUSION: Our patient showed visible improvement with EPI-743 treatment and the only patient surviving after 4years. There is a possibility that EPI-743 is modifying the natural course of the syndrome.
Authors: Juan M Suárez-Rivero; Carmen J Pastor-Maldonado; Mario de la Mata; Marina Villanueva-Paz; Suleva Povea-Cabello; Mónica Álvarez-Córdoba; Irene Villalón-García; Alejandra Suárez-Carrillo; Marta Talaverón-Rey; Manuel Munuera; José A Sánchez-Alcázar Journal: Int J Mol Sci Date: 2019-10-20 Impact factor: 5.923
Authors: Juan M Suárez-Rivero; Carmen J Pastor-Maldonado; Suleva Povea-Cabello; Mónica Álvarez-Córdoba; Irene Villalón-García; Manuel Munuera-Cabeza; Alejandra Suárez-Carrillo; Marta Talaverón-Rey; José A Sánchez-Alcázar Journal: Antioxidants (Basel) Date: 2021-02-04