Erythrocyte Encapsulated Thymidine Phosphorylase for the Treatment of Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy: Study Protocol for a Multi-Centre, Multiple Dose, Open Label Trial
| Autor: | Cornelia Kornblum, Sema Kalkan Uçar, Moshe Baru, Agathe Roubertie, Murray D. Bain, Jeanie Price, Marcia Sellos-Moura, Shamima Rahman, Patrick Horn, Philip Sedgwick, Mauro Scarpelli, Lynette D. Fairbanks, Thomas Klopstock, Massimiliano Filosto, Bridget E. Bax, Hanna Mandel, Michelle Levene, Niranjanan Nirmalananthan |
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| Přispěvatelé: | Ege Üniversitesi |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
TYMP
Mitochondrial disease lcsh:Medicine rare disease Pharmacology thymidine phosphorylase Article 03 medical and health sciences chemistry.chemical_compound erythrocyte encapsulated thymidine phosphorylase 0302 clinical medicine medicine ddc:610 orphan disease Thymidine phosphorylase 030304 developmental biology 0303 health sciences mitochondrial neurogastrointestinal encephalomyopathy business.industry lcsh:R General Medicine Enzyme replacement therapy medicine.disease Deoxyuridine Phase II Clinical trial Enzyme replacement Erythrocyte encapsulated thymidine phosphorylase Mitochondrial neurogastrointestinal encephalomyopathy MNGIE Multiple dose Orphan disease Rare disease mitochondrial disease chemistry Tolerability Pharmacodynamics enzyme replacement multiple dose Thymidine business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Clinical Medicine Journal of Clinical Medicine 8(8), 1096 (2019). doi:10.3390/jcm8081096 Journal of Clinical Medicine, Vol 8, Iss 8, p 1096 (2019) Volume 8 Issue 8 |
| ISSN: | 2077-0383 |
| Popis: | WOS: 000483737700026 PubMed ID: 31344955 Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder which primarily affects the gastrointestinal and nervous systems. This disease is caused by mutations in the nuclear TYMP gene, which encodes for thymidine phosphorylase, an enzyme required for the normal metabolism of deoxynucleosides, thymidine, and deoxyuridine. The subsequent elevated systemic concentrations of deoxynucleosides lead to increased intracellular concentrations of their corresponding triphosphates, and ultimately mitochondrial failure due to progressive accumulation of mitochondrial DNA (mtDNA) defects and mtDNA depletion. Currently, there are no treatments for MNGIE where effectiveness has been evidenced in clinical trials. This Phase 2, multi-centre, multiple dose, open label trial without a control will investigate the application of erythrocyte-encapsulated thymidine phosphorylase (EE-TP) as an enzyme replacement therapy for MNGIE. Three EE-TP dose levels are planned with patients receiving the dose level that achieves metabolic correction. The study duration is 31 months, comprising 28 days of screening, 90 days of run-in, 24 months of treatment and 90 days of post-dose follow-up. The primary objectives are to determine the safety, tolerability, pharmacodynamics, and efficacy of multiple doses of EE-TP. The secondary objectives are to assess EE-TP immunogenicity after multiple dose administrations and changes in clinical assessments, and the pharmacodynamics effect of EE-TP on clinical assessments. Medical Research CouncilMedical Research Council UK (MRC) [K025406]; Orphan Technologies This study is funded by the Medical Research Council (K025406) and Orphan Technologies. |
| Databáze: | OpenAIRE |
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