期刊
JOURNAL OF CLINICAL MEDICINE
卷 8, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/jcm8040457
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
资金
- United Mitochondrial Disease Foundation [08-004]
- Purine Metabolic Patients Association
- Medical Research Council Development Pathway Funding Scheme [GO90217, K025406]
- MRC [MR/K025406/1, G0902179, G0800674, MR/J010448/1] Funding Source: UKRI
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.
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