© 2015 Informa UK, Ltd. Introduction: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in TYMP, which encodes thymidine phosphorylase (TP). TP dysfunction leads to systemic overload of thymidine (dThd) and deoxyuridine (dUrd), and altered mitochondrial deoxyribonucleotide homeostasis, which interferes with mitochondrial DNA replication and results in mitochondrial dysfunction. In MNGIE, the clinical phenotype is the consequence of an accumulation of noxious metabolites.Areas covered: Knowledge gained about the pathomechanisms involved in MNGIE has allowed the design of plausible treatments aimed to clear the systemic dThd and dUrd overload. This article describes these strategies, from the first attempts to treat the disease through dialysis, to allogeneic hematopoietic stem cell transplantation (allo-HSCT), which has been the most successful treatment in the long term to date. This option, however, is associated with a high risk of severe adverse effects so safer alternatives with long-term efficacy are required such as gene therapy.Expert opinion: The generally poor health of MNGIE patients at the time of treatment aggravates the risks associated with therapies like allo-HSCT. Recently, gene therapy has emerged as a feasible alternative, based on promising preclinical results. To this end, clinical trials should be carefully designed and carried out to investigate the safety and efficacy of this option.
- adeno-associated virus
- gene therapy
- mitochondrial neurogastrointestinal encephalomyopathy
- thymidine phosphorylase