Safety and Efficacy of Erythrocyte Encapsulated Thymidine Phosphorylase in Mitochondrial Neurogastrointestinal Encephalomyopathy

Journal of Clinical Medicine

Massimiliano Filosto¹  Dario Pacitti²  NicholasF. Moran³  AndrewD. MacKinnon⁴  Niranjanan Nirmalananthan⁴  Hanna Mandel⁵  MurrayD. Bain⁶  Michelle Levene⁶  BridgetE Bax⁶  Mauro Scarpelli⁷  Joanna Poulton⁸  Lynette Fairbanks⁹ 

[1] Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy;College of Medicine and Health, St Luke’s Campus, University of Exeter, EX1 2LU, UK;Department of Neuroscience, East Kent Hospitals Foundation Trust, Canterbury, CT1 3NG, UK;Departments of Neurology and Neuroradiology, Atkinson Morley Regional Neurosciences Centre, St George’s Hospital, London, SW17 0QT, UK;Galilee Medical Center, Nahariya 22100, Israel;Molecular and Clinical Sciences, St. George’s, University of London, London, SW17 ORE, UK;Neurology Unit, Azienda Ospedaliera Universitaria Integrata Verona, Piazzale Aristide Stefani, 1, 37126 Verona, Italy;Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, OX3 9DU, UK;The Purine Research Laboratory, St Thomas’ Hospital, London SE1 7EH, UK;

关键词: Mitochondrial neurogastrointestinal encephalomyopathy;    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE);    nuclear thymidine phosphorylase gene (TYMP);    enzyme replacement;    thymidine phosphorylase;    mitochondrial disease;    rare disease;    orphan disease;   

DOI  :  10.3390/jcm8040457

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown