NEW HORIZONS IN THE TREATMENT OF MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOMYOPATHY (MNGIE): FROM PATHOGENESIS TO THERAPIES

Mitochondrial neurogastrointestinal encephalomyopathy syndrome (MNGIE), also known as mitochondrial gastrointestinal encephalopathy, is an extremely rare hereditary metabolic disorder caused by mutations in the nuclear gene TYMP, which encodes the enzyme thymidine phosphorylase (TP). The subsequent systemic accumulation of deoxyribonucleosides leads to mutations in the mitochondrial genetic material and ultimately to the failure of the organelle itself. The degenerative nature of the disease and the intricate nature of its clinical symptoms effectively hinder proper diagnosis, which, with the life expectancy of MNGIE patients estimated at 37 years, significantly complicates its treatment. Currently, available therapeutic approaches, based on symptomatic treatment, are slowly giving way to newly developed experimental therapies. In vitro and in vivo models have played a key role in this topic, contributing to the deepening and understanding of the disease mechanisms over the years, thus providing an important foundation for further research and potential therapies. This review provides a comprehensive overview of the current state of knowledge on MNGIE, with a focus on current therapeutic options, available disease models, and diagnostic procedures. This review aims to increase clinical awareness and support the development of more effective treatments and diagnostics, as well as to provide valuable information that can improve the quality of life and care of patients with MNGIE.