LONDON – The UK government has taken a significant step forward in legalizing the use of mitochondria donation to prevent inherited mitochondrial diseases, publishing draft regulations for consultation.

The draft will now be open for public comment until May, following which the final proposals will be debated by parliament. The move came as the use of mitochondria donation was put under the microscope in the U.S., at a two-day FDA advisory committee meeting. (See BioWorld Today, Feb. 27, 2014.)

This will be the second time the UK public has been asked for its opinion, with a consultation from 2012 showing there is overall support for the use of mitochondria replacement to prevent the inheritance of the serious disorders that arise from defects in mitochondria genes.

Following the earlier consultation, the government announced in July 2013 that it would legislate to allow mitochondria donation; this latest consultation concerns the detail of the regulations that will be put in place to govern the use of the technique.

Mitochondria replacement is controversial because it would result in children born with DNA from three people, with girls having genetic changes to their germlines that would be inherited by any subsequent female offspring.

It is estimated that one in 200 children born each year in the UK have some form of mitochondrial disorder. The main effect is to prevent the proper functioning of mitochondria, leaving cells unable to generate sufficient energy.

The impact can be manifest in a number of ways including NARP (neuropathy, ataxia and retinitis pigmentosa), a condition consisting of various symptoms affecting the nervous system, including numbness or pain in the limbs, muscle weakness, problems with balance and coordination, and loss of vision; Leigh syndrome, a degenerative disorder affecting the brain and nervous system; and Leber’s hereditary optic atrophy, which causes blindness.

It is true that mitochondria donation would result in “the genetic alteration of disease risk” and should not be taken lightly, said Peter Braude, emeritus professor of obstetrics and gynaecology at King’s College London. But its use will be limited to couples who “know from sad experience” the effects of mitochondrial disease and are best placed to understand the risks of the technology, he said.

Although pleased to see progress, patients’ group are getting impatient. “It will soon be two years since the initial consultation with the public was announced and three years since the review began. There have been lengthy waits at every stage,” said Robert Meadowcroft, chief executive of the Muscular Dystrophy Campaign, urging the government to ensure the legislation is passed before the next national election in May 2015.

Jeremy Farrar, director of the medical charity the Wellcome Trust agreed saying, “We urge the government to move swiftly, so that parliament can debate the regulations at the earliest opportunity and families affected by these devastating disorders can begin to benefit.”

Under UK law, replacing mitochondria currently is illegal and the move to introduce regulations to allow the technique is unusual in having been made in advance of the technology being available.

Certainly, the view among experts who gave evidence to the FDA advisory committee meeting was that while mitochondria donation has been shown to work in animal studies, the technique is not ready for the clinic.

The 27 mitochondria genes, inherited solely from the mother, account for less than 0.2 percent of human DNA and are entirely separate from the genes in the cell nucleus. Two approaches are in development to allow the in vitro fertilization of embryos without defects in those genes.

Pro-nuclear transfer involves removing the nucleus from a fertilized egg (regarded as an embryo under UK law) that has defective mitochondria and transferring it into a donated egg that has healthy mitochondria and has had its nucleus removed.

Maternal spindle transfer involves transferring the maternal nuclear DNA from the mother’s egg into a donor egg with healthy mitochondria, from which the donor’s nuclear DNA has been removed. The egg is then fertilized by the father’s sperm.

The Wellcome Trust awarded an $8.8 million grant to researchers at Newcastle University in January 2012 to work on optimizing the technology.

A UK scientific and safety review published in December 2012 concluded there was no evidence to conclude either technique was unsafe, but that there was insufficient research to recommend one over the other. In the draft proposals published last week, the government said it would conduct a further review of the science before the legislation is put before parliament.

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