Using mRNA to tackle ultra-rare mitochondrial disease

There’s about a one in a million chance that a baby will be born with Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE).

The rarity of the condition does not change the fact it is fatal.

Now, with a grant of about $150,000 from the UK-based Lily Foundation, University of Cambridge Neurologist Dr Jelle van den Ameele and AIBN group leader Dr Seth Cheetham are hoping to change that.

Together with Dr Ramon Marti from Vall D’Hebron Institut de Recerca in Barcelona, Dr Cheetham and Dr van den Ameele will be attempting to develop and evaluate a novel mRNA-based gene therapy for MNGIE.

MNGIE cases involve mutations affecting the enzyme Thymidine Phosphorylase (TP), which can lead to considerable digestive system impairments, including vomiting, nausea, diarrhea, abdominal pain, and malnutrition. 

Dr Cheetham says current treatments involve liver- or stem-cell-transplantation, which are associated with significant limitations and risks.

“But advances mRNA technology mean we have unprecedented opportunities to find new solutions,” he says. 

“It also means that, if successful, mRNA technology could also help us address a wider range of mitochondrial diseases down the track”.

Dr Cheetham is deputy director of the AIBN’s BASE mRNA facility, which has become Australia’s leading provider of mRNA for research and pilot studies and since its launch in 2021.

The specific objective of the Lily Foundation project is to obtain first proof-of-concept data for TYMP mRNA-based liver-targeted gene therapy, by testing biochemical efficacy in a genetic MNGIE mouse model.

The results from these in vitro and in vivo studies will provide essential data, required for larger-scale funding applications to support further pre-clinical toxicity studies and to initiate regulatory applications for a future clinical trial.

“The success of the COVID-19 vaccines has accelerated the development of mRNA-based therapeutics for a variety of diseases and disorders,” Dr Cheetham said.

“The hope is that mRNA can help us again here.”

The Lily Foundation was created in 2007 and is the UK's leading mitochondrial disease charity.

You can read more about the work of the Lily Foundation here.