Prospective therapeutic approaches in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)

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 e...