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UK clinics may be able to offer mitochrondrial donation next spring

BMJ 2016; 355 doi: https://doi.org/10.1136/bmj.i6492 (Published 01 December 2016) Cite this as: BMJ 2016;355:i6492
  1. Nigel Hawkes
  1. London

A scientific panel has given the go ahead for use of mitochondrial donation in carefully selected women to improve their chances of having children free of inherited mitochondrial diseases.1

The technique involves substituting healthy mitochondrial DNA from a donor egg for the abnormal version carried by the mother’s eggs, before or after the egg has been fertilised. The resulting embryo, with nuclear DNA from the mother and the father and mitochondrial DNA from the donor, is then implanted in the mother’s womb.

The Human Fertilisation and Embryology Authority set up the panel after parliament last year approved the use of two techniques for mitochondrial donation.2 3 4 5 The panel’s remit was to advise whether the procedures were ready for clinical application. It has determined that they are, subject to some caveats.

The report will now go to the authority for consideration at a meeting on 15 December. If it agrees, in vitro fertilisation (IVF) clinics will be able to apply for a licence to perform the procedure. Those granted a licence will then have to submit case by case justifications for each patient they want to treat.

Approval for the first case could be reached as soon as March or April 2017, with the clinic at the University of Newcastle, a leading centre for the research, being the most likely choice.

However, some questions remain unanswered. Choosing his words carefully, Andy Greenfield, the panel’s chairman, told a briefing at the Science Media Centre in London, “We recommend that the stage has been reached for cautious clinical use as a risk reduction strategy in carefully selected patients.” The panel’s report says that mitochondrial donation should be used only where inheritance of the disease is likely to cause death or serious disease and no acceptable alternatives are available.

Possible alternatives include the donation of an entire egg rather than just the mitochondrial part, but that would result in children who were not genetically the offspring of the mother, which some women find unacceptable. A second alternative that can be used in some cases is preimplantation genetic diagnosis, useful where the proportion of defective mitochondria is low and where it is possible to select, before implantation, embryos that do not include such defects. But this does not apply to all would-be mothers.

A healthy baby has already been born after use of one of the techniques approved by parliament, according to claims made in September by the US team responsible. The procedure has not been approved in the United States, so the team, led by John Zhang of the New Hope Fertility Centre in New York City, went to Mexico to carry it out.

Mitochondrial disorders are not uncommon, Frances Flinter of Guy’s and St Thomas’ NHS Foundation Trust told the briefing. As many as one in 200 women may have some damaged mitochondrial DNA but too little to do major harm. One in 10 000 women may carry sufficient damage to cause clinical disease in her children, often resulting in an early death. Flinter estimated that there may be 3500 women in the UK who could benefit from mitochondrial donation.

The greatest uncertainty is that the transformed embryos can in some cases “revert” to a damaged condition by a process that is not fully understood. Experiments with stem cells derived from transformed embryos indicate that reversion can occur in about one in five cases. Robin Lovell-Badge of the Francis Crick Institute, a member of the panel, said that the chances of reversion could be reduced by minimising the number of damaged mitochondria carried over from the patient’s egg to that of the donor. With care, he believed that the proportion could be as low as 1%.

“The technique is not perfect: there is a chance of something going wrong,” he said. “But it could, in the great majority of cases, enable affected women to have healthy babies. The Mexico baby looks OK, but that’s only one case. We recommend that all babies conceived in this way should have prenatal checks. Then, if reversion is detected, a termination could be offered.”

The report was generally welcomed by outside experts. Bert Smeets of the Genome Centre at Maastricht University called it historic. “I admire how these decisions are being made in the UK,” he said. “It is a very careful and thorough process but also open to the general public, allowing a decision which might not be supported by everybody but which certainly will be respected by everybody.

“It makes sense to limit the application of mitochondrial donation to patients who do not have an alternative in prenatal diagnosis or preimplantation genetic diagnosis. This may seem obvious; but as shown by the recent report on a successful application of mitochondrial donation in Mexico, this is not always the case, as preimplantation genetic diagnosis could have been applied in that situation as well.”

Mary Herbert, professor of reproductive biology at Newcastle, said, “Once we get the green light from the Human Fertilisation and Embryology Authority, we are ready to submit an application for a licence to offer mitochondrial donation treatments here at Newcastle Fertility Centre. This will form part of a comprehensive programme of NHS funded treatment for families affected by mitochondrial DNA disease.

“It is really gratifying for us to be able to extend the scope of reproductive technologies to help families affected by these dreadful diseases, and it will be a great privilege to see our work over the past decade finally come to fruition.”

References

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