You are here: MDDS: vital research into a rare disease

Why is this research important?

Mitochondria are the powerhouses of our cells, performing the essential job of generating the energy our bodies need to function. If certain genes that are involved in making the mitochondria’s own DNA are faulty, this affects our body’s energy supply. That can have disastrous consequences for organs that need lots of energy, such as the brain, muscle and the liver.

Around one in five children with mitochondrial DNA depletion syndrome (MDDS) have a severe type that is caused by faults in a gene called DGUOK. They will experience progressive liver disease and neurological symptoms.

“A liver transplant can help save some children from liver failure but it does not improve or prevent their brain disease. Sadly, there is no cure for MDDS and most children will ultimately lose their lives at a very young age,” explains Dr Keshavan. 

Research aims

Dr Nandaki Keshavan has been awarded an Action Research Training Fellowship to embark on a three year study at UCL Great Ormond Street Institute of Child Health.

He is carrying out a preclinical study that aims to develop the first gene therapy treatment for MDDS – a treatment that could help produce a cure. Dr Keshavan’s research could also help develop similar treatments for other mitochondrial diseases, reaching even more children facing this terrible disease.

“Our goal is to use gene therapy to cure children with a severe form of MDDS.”
Dr Keshavan

Research approach

Gene therapy has been applied to other rare disorders with success in both preclinical and clinical studies, but it has not yet been trialled in treating DGUOK deficiency.

Gene therapy involves the correction of genetic abnormality by delivering a ‘correct’ copy of the affected gene to cells. The researchers will use specially designed carriers to deliver a correct copy of the DGUOK gene into liver and brain cells in the laboratory. The team will also investigate the best dose, administration route and timing of treatment to optimise beneficial effects.

Clinical impact

If this study shows that mitochondrial gene therapy is an effective form of treatment, it will lay the foundation for future clinical trials in patients and take us one step closer to finding a cure for DGUOK MDDS.

In the future, the researchers also expect to broaden their use of gene therapy to other genetic causes of MDDS and to mitochondrial diseases in general, which will help a larger number of seriously affected children.

"There is an urgent need to find effective new treatments, which would give hope to children and their families who are affected by this devastating condition," says Dr Keshavan