Researcher prize and $200,000 for worm research that could help treat rare genetic child diseases

The ground breaking research will investigate the potential of new molecules invented at the University of Exeter to restore normal metabolic activity in primary mitochondrial diseases (PMD) such as Leigh Syndrome. Mitochondria are the “power plant” of the cell, turning nutrients from food into metabolic energy (ATP) but in Leigh Syndrome and other diseases in the group, the ability of mitochondria to do this is greatly reduced, resulting in injury to the brain, lungs, heart, central nervous system and muscle. These disorders primarily effect young children and with no effective therapies available. The children rarely reach adulthood and there is an urgent need to identify and develop new drugs to treat these conditions.

Professor Matt Whiteman from the University of Exeter Medical School has now won the Experienced Principal Investigator Prize and secured $200,000 from The United Mitochondrial Disease Foundation in the USA to use new molecules invented at Exeter to “recharge” the defective mitochondria in PMD. Teaming up with Dr. Tim Etheridge, a Senior Lecturer at the Department of Sports and Health Sciences at Exeter, the research will use the microscopic worm C. elegans as a model system to rapidly identify drug potential.

The University of Exeter-invented compounds specifically target mitochondria with minute quantities of the gas hydrogen sulfide. This gas has historically been considered highly toxic, but human cells can use minute quantities to regulate mitochondrial activity, and importantly generate ATP. This might seem surprising, but when life first emerged on earth hydrogen sulfide, rather than oxygen, was the dominant gas in the atmosphere yet life thrived for billions of years by using this gas as a metabolic fuel. Throughout evolution, human cells have maintained this ability and the Exeter compounds work by mimicking this ancient process.

Professor Whiteman and his colleagues have previously these novel compounds are therapeutically effective in animal models where mitochondrial dysfunction is a result of the disease process. These studies are very promising for PMD where the mitochondrial defect is a direct cause of the disease.

Dr Tim Etheridge said: “We were really excited to take our research in this new direction, into these devastating and frequently overlooked rare conditions. By using worms we can model the mitochondrial defects in PMD in a whole organism and very quickly identify molecules which may then be taken forward and developed into drug treatments”. Prof. Whiteman added “We were fortunate to obtain a small grant from the Northcott Devon Medical Foundation to obtain proof-of-principle data to then go to the UMDF for larger scale funding. In that work we were able to show that our first compound, AP39, could increase health span, muscle function, movement and overall wriggliness in worms with mitochondrial defects similar to those seen in some Leigh Syndrome patients”. Initial studies from this work were presented at the United Mitochondrial Disease Foundation in Washington DC, USA earlier this week.

Alison Maguire, Head of Research at The Lily Foundation, said: “'Mitochondrial diseases are amongst the most complex of all inherited genetic diseases and we currently have very few effective therapeutic options for managing the condition. The disease is relentlessly progressive and results in significant illness and early death for both children and adults.

“Professor Whiteman’s research is both exciting and innovative, and if successful, could potentially provide a novel therapeutic option for these families which would be an incredible step forward.”

The University of Exeter has added to this award by providing over £30,000 towards a PhD student to support this work, under its Diamond Jubilee Doctoral Fellowship Match fund scheme.