mRNA-LNP-based gene therapy for Mitochondrial DNA maintenance disorders

Summary

We aim to develop and evaluate a novel therapy for mitochondrial DNA maintenance disorders, mainly focused on Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE). MNGIE is an ultra-rare fatal disease, caused by mutations affecting the enzyme Thymidine Phosphorylase (TP).

Project aims

TP breaks down waste-products of DNA-metabolism, which accumulate in MNGIE, leading to toxicity and clinical manifestations. Current treatments are liver- or stem-cell-transplantation, which are associated with significant limitations/risks. 

Gene-therapy is a promising alternative, but current virus-based approaches are expensive, with potential side-effects. This project aims to test efficacy of a safer and cheaper mRNA-approach in a MNGIE mouse-model. 

This will provide first proof-of-concept for mRNA-therapy in mitochondrial disease, and inform pre-clinical/clinical studies. 

The project is currently funded by the Lily Foundation, in collaboration with Dr Seth Cheetham at the University of Queensland, Australia (see: https://www.thelilyfoundation.org.uk/news/funding-research-and-finding-hope-for-mngie-patients/). 

Contact details

Dr Jelle van den Ameele (jv361@cam.ac.uk) Neurology and Mitochondrial Biology Unit  

Opportunities

This project is open to applicants who want to do a:

• PhD
• MPhil