TY - JOUR
T1 - EPI-743 reverses the progression of the pediatric mitochondrial disease-Genetically defined Leigh Syndrome
AU - Martinelli, Diego
AU - Catteruccia, Michela
AU - Piemonte, Fiorella
AU - Pastore, Anna
AU - Tozzi, Giulia
AU - Dionisi-Vici, Carlo
AU - Pontrelli, Giuseppe
AU - Corsetti, Tiziana
AU - Livadiotti, Susanna
AU - Kheifets, Viktoria
AU - Hinman, Andrew
AU - Shrader, William D.
AU - Thoolen, Martin
AU - Klein, Matthew B.
AU - Bertini, Enrico
AU - Miller, Guy
PY - 2012/11
Y1 - 2012/11
N2 - Background: Genetically defined Leigh syndrome is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. No treatment is available. EPI-743 is a novel small molecule developed for the treatment of Leigh syndrome and other inherited mitochondrial diseases. In compassionate use cases and in an FDA Expanded Access protocol, children with Leigh syndrome treated with EPI-743 demonstrated objective signs of neurologic and neuromuscular improvement. To confirm these initial findings, a phase 2A open label trial of EPI-743 for children with genetically-confirmed Leigh syndrome was conducted and herein we report the results. Methods: A single arm clinical trial was performed in children with genetically defined Leigh syndrome. Subjects were treated for 6. months with EPI-743 three times daily and all were eligible for a treatment extension phase. The primary objective of the trial was to arrest disease progression as assessed by neuromuscular and quality of life metrics. Results were compared to the reported natural history of the disease. Results: Ten consecutive children, ages 1-13. years, were enrolled; they possessed seven different genetic defects. All children exhibited reversal of disease progression regardless of genetic determinant or disease severity. The primary endpoints-Newcastle Pediatric Mitochondrial Disease Scale, the Gross Motor Function Measure, and PedsQL Neuromuscular Module-demonstrated statistically significant improvement (p
AB - Background: Genetically defined Leigh syndrome is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. No treatment is available. EPI-743 is a novel small molecule developed for the treatment of Leigh syndrome and other inherited mitochondrial diseases. In compassionate use cases and in an FDA Expanded Access protocol, children with Leigh syndrome treated with EPI-743 demonstrated objective signs of neurologic and neuromuscular improvement. To confirm these initial findings, a phase 2A open label trial of EPI-743 for children with genetically-confirmed Leigh syndrome was conducted and herein we report the results. Methods: A single arm clinical trial was performed in children with genetically defined Leigh syndrome. Subjects were treated for 6. months with EPI-743 three times daily and all were eligible for a treatment extension phase. The primary objective of the trial was to arrest disease progression as assessed by neuromuscular and quality of life metrics. Results were compared to the reported natural history of the disease. Results: Ten consecutive children, ages 1-13. years, were enrolled; they possessed seven different genetic defects. All children exhibited reversal of disease progression regardless of genetic determinant or disease severity. The primary endpoints-Newcastle Pediatric Mitochondrial Disease Scale, the Gross Motor Function Measure, and PedsQL Neuromuscular Module-demonstrated statistically significant improvement (p
KW - EPI-743
KW - Leigh syndrome
KW - Mitochondrial disease
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UR - http://www.scopus.com/inward/citedby.url?scp=84867897915&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2012.09.007
DO - 10.1016/j.ymgme.2012.09.007
M3 - Article
C2 - 23010433
AN - SCOPUS:84867897915
VL - 107
SP - 383
EP - 388
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
SN - 1096-7192
IS - 3
ER -