New transplant technique to treat mitochondrial myopathy

Funded by the Muscular Dystrophy Campaign, Professor Turnbull and his team at the University of Newcastle are developing a technique which in time might be used to prevent the transmission of mitochondrial myopathies from one generation to the next.

Contents:

• What is mitochondrial myopathy?
• What is the new technique?
• Statement from Marita Pohlschmidt, Director of Research at the Muscular Dystrophy Campaign

What is mitochondrial myopathy?

Mitochondrial myopathies are a group of diseases that affect approximately 6,000 people in the UK. The condition is caused by a genetic defect in mitochondria which are the ‘powerhouses’ of the cells by converting the food we eat into energy. Every cell has thousands of mitochondria and if they do not function properly, it can lead to severe muscle weakness and wasting.

Mitochondria have their own piece of DNA which accounts for approximately 0.0005% of the entire genetic information in a cell. Every individual inherits the mitochondria from the mother and this is the reason why mitochondrial myopathies are passed on through the maternal line.

People with mitochondrial myopathy generally carry a mixture of ‘defective’ (mutant) and ‘healthy’ mitochondria in their cells and the severity of the disease is determined by their ratio. The ratio however, varies from cell to cell and this makes it difficult for clinicians to provide genetic counselling or give an accurate prenatal diagnosis or pre-implantation diagnosis.

What is the new technique?

Professor Doug Turnbull and his team are currently developing a technique that combines IVF with ‘cell surgery’ and that is aimed to prevent the transmission of the condition from the mother to a future child. This involves transplanting the nucleus (which contains all the 99,9995% of other genetic information in cell) from an egg that contains defective mitochondria to another egg (from which the nucleus has been removed), which only contains healthy mitochondria. The technique has been tested in an animal model and the mice generated do not show any signs of mitochondrial disease.

The team around Professor Turnbull presented results of preliminary work last week at the ‘Inaugural Neuromuscular Conference’ in London that was organised by the Muscular Dystrophy Campaign in partnership with the new MRC Centre for Translational Research in London. They could show that the technique works in experiments with abnormal human embryos, a side product of fertility treatment. They successfully applied the technique to 10 one-cell embryos and monitored their development for up to five days.

The team in Newcastle had previously been given permission by The Human Fertilisation and Embryology Authority to develop this technique in the laboratory, but current legislation does not allow them to use this method in clinic. Lord Walton of Detchant has tabled amendments to the Human Fertilisation and Embryology Bill that would allow the Newcastle team to apply the technology in clinic without seeking permission of Parliament, but by seeking approval of the Human Fertilisation and Embryology Authority instead.

The amendment was rejected by the Government on Monday, but Lord Walton was assured that the matter will be debated and will be given ‘full public consideration’.

“We are hoping to do this in the next three years,” says Professor Turnbull. “We don’t then want to wait another three years for the law to change.”

Statement from Marita Pohlschmidt, Director of Research at the Muscular Dystrophy Campaign

“Mitochondrial myopathy can be a devastating disease for which there is currently no treatment available. The inheritance is very complex which makes it difficult for clinicians to advise parents how severely a child will be affected. The Muscular Dystrophy Campaign has funded the research carried out by Professor Turnbull and his team for many years and we hope that the technology developed in Newcastle will in time, give families the option to plan their future and have children not affected by this condition.

“We urge the Government to pay close attention to the issues raised by Lord Walton of Detchant in the House of Lords. His amendments addressed the need for a regulatory framework to enable researchers to make a swift ‘bench-to-bedside’ transfer of this promising technology.”