Safety and efficacy of erythrocyte encapsulated thymidine phosphorylase in mitochondrial neurogastrointestinal encephalomyopathy
| Autor: | Andrew D. Mackinnon, Niranjanan Nirmalananthan, Mauro Scarpelli, Joanna Poulton, Nicholas Moran, Bridget E. Bax, Dario Pacitti, Murray D. Bain, Hanna Mandel, Lynette D. Fairbanks, Michelle Levene, Massimiliano Filosto |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Mitochondrial disease
lcsh:Medicine rare disease Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) Pharmacology thymidine phosphorylase Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine orphan disease Thymidine phosphorylase Adverse effect 030304 developmental biology 0303 health sciences business.industry lcsh:R General Medicine Enzyme replacement therapy medicine.disease Deoxyuridine nuclear thymidine phosphorylase gene (TYMP) Enzyme replacement Mitochondrial neurogastrointestinal encephalomyopathy Nuclear thymidine phosphorylase gene (TYMP) Orphan disease Rare disease Discontinuation mitochondrial disease Tolerability chemistry enzyme replacement business Thymidine 030217 neurology & neurosurgery |
| Zdroj: | Journal of Clinical Medicine Volume 8 Issue 4 Journal of Clinical Medicine, Vol 8, Iss 4, p 457 (2019) |
| ISSN: | 2077-0383 |
| Popis: | Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare autosomal recessive disorder of nucleoside metabolism that is caused by mutations in the nuclear thymidine phosphorylase gene (TYMP) gene, encoding for the enzyme thymidine phosphorylase. There are currently no approved treatments for MNGIE. The aim of this study was to investigate the safety, tolerability, and efficacy of an enzyme replacement therapy for the treatment of MNGIE. In this single centre study, three adult patients with MNGIE received intravenous escalating doses of erythrocyte encapsulated thymidine phosphorylase (EE-TP dose range: 4 to 108 U/kg/4 weeks). EE-TP was well tolerated and reductions in the disease-associated plasma metabolites, thymidine, and deoxyuridine were observed in all three patients. Clinical improvements, including weight gain and improved disease scores, were observed in two patients, suggesting that EE-TP is able to reverse some aspects of the disease pathology. Transient, non-serious adverse events were observed in two of the three patients these did not lead to therapy discontinuation and they were managed with pre-medication prior to infusion of EE-TP. To conclude, enzyme replacement therapy with EE-TP demonstrated biochemical and clinical therapeutic efficacy with an acceptable clinical safety profile. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|