EPI-743 reverses the progression of the pediatric mitochondrial disease—Genetically defined Leigh Syndrome
| Autor: | Guy M. Miller, Fiorella Piemonte, Andrew W. Hinman, Susanna Livadiotti, Martin Thoolen, Anna Pastore, Michela Catteruccia, Matthew B. Klein, Carlo Dionisi-Vici, Diego Martinelli, Enrico Bertini, Viktoria Kheifets, Giulia Tozzi, William D. Shrader, Giuseppe Pontrelli, Tiziana Corsetti |
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| Rok vydání: | 2012 |
| Předmět: |
Compassionate Use Trials
Male Pediatrics medicine.medical_specialty Adolescent Ubiquinone Endocrinology Diabetes and Metabolism Mitochondrial disease Disease Severity of Illness Index Biochemistry Drug Administration Schedule Endocrinology Quality of life Rating scale Genetics medicine Humans Child Adverse effect Molecular Biology business.industry Infant medicine.disease Mitochondria Clinical trial Natural history Child Preschool Expanded access Disease Progression Quality of Life Physical therapy Female Leigh Disease business Psychomotor Performance |
| Zdroj: | Molecular Genetics and Metabolism. 107:383-388 |
| ISSN: | 1096-7192 |
| DOI: | 10.1016/j.ymgme.2012.09.007 |
| Popis: | article i nfo 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 treatedfor6 monthswithEPI-743three timesdaily andall wereeligiblefora treatmentextension 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:Tenconsecutivechildren,ages1-13 years,were enrolled;theypossessedsevendifferentgeneticdefects. 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 (pb0.05). In addition, all children had an improvement of one class on the Movement Disorder-Childhood Rating Scale. No significant drug-related adverse events were recorded. Conclusions: In comparison to the natural history of Leigh syndrome, EPI-743 improves clinical outcomes in children with genetically confirmed Leigh syndrome. |
| Databáze: | OpenAIRE |
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