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It has been established that MNGIE is caused by mutations in the gene encoding thymidine phosphorylase (TP), which lead to absolute or nearly complete loss of its catalytic activity, producing systemic accumulations of its substrates, thymidine (dThd) and deoxyuridine (dUrd). Findings obtained from in vitro and in vivo studies indicate that the biochemical imbalances specifically impair mitochondrial DNA (mtDNA) replication, repair, or both leading to mitochondrial dysfunction. We have proposed that therapy for MNGIE should be aimed at reducing the concentrations of these toxic nucleosides to normal or nearly normal levels. The first treatment, allogeneic stem-cell transplantation (alloSCT) reported in 2006, produced a nearly full biochemical correction of the dThd and dUrd imbalances in blood. Clinical follow-up of this and other patients receiving alloSCT is necessary to determine whether this and other therapies based on a permanent restoration of TP will be effective treatment for MNGIE.<\/jats:p>","DOI":"10.1007\/s10540-007-9043-2","type":"journal-article","created":{"date-parts":[[2007,6,4]],"date-time":"2007-06-04T15:01:17Z","timestamp":1180969277000},"page":"151-163","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Biochemical Features and Therapeutic Approaches"],"prefix":"10.1042","volume":"27","author":[{"given":"M. C.","family":"Lara","sequence":"first","affiliation":[{"name":"Centre d'Investigacions en Bioqu\u00edmica i Biologia Molecular, Institut de Recerca Hospital Universitari Vall d'Hebron and Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, P. 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