LONDON – The U.K. regulator has given the final go-ahead to the use of mitochondrial donation, clearing the way for licenses to be granted early next year and meaning the first child with DNA from three people could be born here toward the end of 2017.

The decision follows a final review of the science, which was commissioned by the Human Fertility and Embryology Authority (HFEA) after mitochondrial donation was given legal approval in February 2015. (See BioWorld Today, Feb. 4, 2015.)

The review, which included a global call for evidence, concluded that despite the potential to prevent inherited mitochondrial diseases, there are risks. Given those risks, the technique should only be used in circumstances in which a woman's level of pathogenic mitochondrial DNA is so high that there is no prospect that a less-affected embryo could be selected using preimplantation genetic diagnosis.

Sally Cheshire, the chair of the HFEA, said, "Today's historic decision means that parents at very high risk of having a child with a life-threatening mitochondrial disease may soon have the chance of a healthy, genetically related child."

After a thorough review of the development, safety and efficacy of the technique, "we feel now is the right time to carefully introduce this new treatment in limited circumstances," Cheshire said.

The first application for a license is expected to be made by Newcastle University, which has a specialist center for mitochondrial disease and also is at the forefront of in vitro fertilization (IVF) research. The university confirmed Thursday that it will apply for a license within 24 hours.

Doug Turnbull, director of the Wellcome Centre for Mitochondrial Research at Newcastle University, said, "We are delighted by today's decision as it paves the way to offering mitochondrial donation as part of a National Health Service [NHS]-funded package of care for families affected by mitochondrial DNA disease."

The Newcastle center will be aiming to treat up to 25 patients a year. It is seeking healthy women, up to age 35, to consider donating their eggs. Donors will be required to attend clinics for close monitoring and, therefore, are encouraged to live in the North East region.

The center will also do long-term follow up of any children born as a result.

The NHS announced it will make up to £8 million ($US9.9 million) available over five years to fund the treatment costs of a five-year clinical trial of mitochondrial donation. James Palmer, clinical director of specialized services, said, "Mitochondrial diseases can be devastating and life-limiting as well as hugely costly to the NHS to treat. This trial will, for the first time, give women living with mitochondrial disease the option of having a baby without passing on their condition."

Although the U.K. is the first country to have legislation allowing mitochondrial donation, the first child known to be born following use of the technique was delivered at a clinic in Mexico in April.

That procedure was carried out by researchers based at the New Hope Fertility Center in New York, led by the center's medical director, John Zhang. The researchers took advantage of the fact that while there is no specific legislation to allow it – or any regulatory oversight – mitochondrial donation is not illegal, as is the case in the U.S. (See BioWorld Today, Sept. 29, 2016.)

Zhang said he received the approval of an institutional review board, but he was criticized for remarks he made about Mexico's medical regulations when the birth became world news.

That prompted him to contact all journalists who covered the story, saying he was "deeply saddened and concerned" his remarks had been "misunderstood" and apologizing to the Mexican government.

"Mexico's regulations are in many ways highly advanced, allowing us to pursue this area of fertility medicine," Zhang wrote.

Regulated system 'preferable' for trials

The HFEA in the U.K. has been laying the path to its final conclusion since 2008. The most recent scientific review of developments in preclinical research, published at the end of November, was the fourth investigation it has commissioned.

The latest look at the science included a videoconference with Zhang and discussions with other U.S. experts. It found that significant progress has been made in addressing remaining issues that were identified in the three previous reports.

It is now the case that embryos generated either by maternal spindle transfer or by pronuclear transfer using enucleated donor eggs, develop to blastocyst stage with efficiencies and a quality comparable to those obtained by standard IVF procedures.

There is no evidence that either of the two techniques is any better or worse than the other; however, pronuclear transfer is more refined in the U.K.

The carryover of mitochondrial DNA from the nuclear DNA of an affected woman is "reassuringly low," at less than 2 percent, the review said.

Frances Flinter, professor in clinical genetics at Guy's and St Thomas' hospital in London and one of the members of the fourth scientific review group, said, "I am delighted that the HFEA is willing to consider license applications now. It is infinitely preferable that the early clinical trials should be done in a tightly regulated system in the U.K., with long-term follow-up of any children born, rather than in countries where there is no regulation or oversight."