Medical charities are urging the UK government to push forward with legislation allowing three-parent IVF treatments to avoid passing on mitochondrial disease. This follows a recent review that found while two such methods were not unsafe, more research should be done to show they are safe for clinical use.
A child inherits DNA from three sources, most of it is nuclear DNA from the biological mother and the biological father, but a small amount is mitochondrial DNA from the mother only. Mitochondria are the power-houses inside cells. They have their own DNA that is separate from that in the nucleus of cells.
Unfortunately, some variants of mitochondrial genes cause diseases, ranging from mild to severe and deadly, and these are passed onto children through their biological mother’s DNA.
IVF is a fertility treatment that removes eggs from the mother’s body and fertilizes them with the father’s sperm in a “test tube”. A number of fertilized eggs are then implanted in the mother’s womb.
It is possible to have a form of IVF called “mitochondrial transfer” which prevents a mother who carries the risky mitochondrial DNA from passing it on, by bringing in a third donor “parent”, a woman who gives her eggs. These eggs are stripped of their nuclei, so the three-parent embryo has most of the DNA (the nuclear DNA) from the mother and the father, and a small amount of DNA (the mitochondrial DNA), from the egg donor.
In February 2011, the Human Fertility and Embryology Authority (HFEA), an independent regulator for fertility treatment in the UK, agreed to carry out a review into the “effectiveness and safety of mitochondrial transfer” at the invitation of the Department of Health (DH).
They assembled a panel of experts, chaired by Professor Neva Haites of the University of Aberdeen and Professor Peter Braude of Kings College London, to carry out the review. They reported their findings to the DH on 18 April.
The HFEA concluded that based on the available evidence, two IVF methods, maternal spindle transfer and pronuclear transfer, were “potentially useful” for a defined group of parents who could pass on a “severe or lethal genetic disease” if they tried to conceive naturally, and who have no other means of having their own genetic child.
In maternal spindle transfer, the nuclear DNA from the mother is inserted into the emptied donor egg and then the egg is fertilized with the father’s sperm. In pronuclear transfer, the mother’s egg is fertilized with the sperm first, and then the nucleus of the fertilized egg is transferred to the empty donor egg. In both cases, the embryo inherits mitochondrial DNA only from the healthy egg donor.
The HFEA panel said that while they found no evidence that these two methods would be unsafe, they recommended a number of experiments to overcome any safety concerns.
The decision to go ahead and progress to full human trials and eventually treatment now rests with Health Secretary Andrew Lansley.
It is to him that leading medical research charities, including the Wellcome Trust, have signed an open letter, urging the government to introduce regulations to allow the methods to be used in clinical treatment.
As a result of amendments to the Human Fertilisation and Embryology Act 1990, the goverment can pass regulations that allow the methods to be used in IVF, but only if they are effective and safe.
Professor Doug Turnbull and his team at Newcastle University is leading research into the pronuclear IVF method. He told the press they were pleased to receive the HFEA endorsement of their work, and they have already started working on some of the experiments they recommended. However, he warned it will take time, and made a special plea for donors:
“Our work relies on the generosity of donors who provide eggs for us to use in our research. This is the major limiting factor for our work. We would like to encourage more donors to come forward so that we can make rapid progress towards a treatment for these diseases,” said Turnbull.
The Wellcome Trust, one of the signatories of the letter to the Health Secretary, is also one of the charities that sponsors Turnbull’s research. Their Director, Sir Mark Walport, also welcomed the HFEA report:
“Mitochondrial diseases are often devastating for patients and their families, but the ability to prevent their transmission is within our reach. It is our duty to these families to do all we can to enable them to raise a family unaffected by mitochondrial disease,” said Walport.
“Professor Turnbull and colleagues would like to carry out the necessary research as requested by the HFEA. We urge the Secretary of State to provide assurances that regulatory amendments will be forthcoming to enable this work to be used in the clinic,” he added.
More info on HFEA report: “Review of scientific methods to avoid mitochondrial disease.”
Note: this article has been amended to correct information about how mitochondrial DNA is passed on in normal reproduction.
Sources: Wellcome Trust, HFEA, Newcastle University, New Scientist.
Written by: Catharine Paddock, PhD