Eight UK babies born from mitochondrial donation, but Australia’s trial faces roadblocks
Britain has announced the births of the first babies born after mitochondrial donation – but a key clinical trial in Australia is yet to begin.
Australian scientists leading a proposed clinical trial testing a radical new IVF procedure are hailing the announcement of the birth of eight babies in the UK after mitochondrial donation as providing vital impetus for the fast-tracking of the research in Australia.
A decade after the UK became the first country in the world to legalise and regulate mitochondrial donation – which uses genetic material from three people – British scientists have reported the births of the eight babies using the technique.
This first major scientific paper on the British program provides critical insight into its effectiveness in preventing transmission of key genetic mutations.
In the UK, the mitochondrial donation treatment program is available to people who are at high risk of passing on mitochondrial disease to their children.
“These findings give grounds for optimism,” said Britain’s Newcastle University professor Mary Herbert, who is now professor of reproductive biology at Monash University in Melbourne.
“As far as we can see from the evidence so far, this technique is effective.”
Monash University scientists, who have been granted $15m from the Australia’s Medical Research Future Fund to develop the technology in an Australian clinical trial, are pointing to the British results as providing an evidence base that they can employ to advance their own research.
But two years after the awarding of the grant, the mitoHOPE clinical trial has been prevented from progressing in Australia by regulators who held a range of ethical and clinical concerns and have not yet granted an initial research licence to the Monash team.
The British study, published in the New England Journal of Medicine, reported eight births and one ongoing pregnancy in 22 patients who underwent pronuclear transfer. The carry-over of unhealthy mitochondria was undetectable or below 5 per cent in six newborns, but two newborns had a larger carry-over of pathogenic mitochondria from the mother; in one of the babies it was 16 per cent.
Carry-over of 18 per cent is considered the threshold for mild disease.
One of the key concerns of critics of mitochondrial donation is that the procedure may not be effective in preventing the transmission of disease from generation to generation in all cases, especially considering that levels of diseased mitochondria in tissues can increase over time.
“I think this technique definitely is risk reduction as it stands,” Professor Herbert said.
“We can’t guarantee prevention, and that really does need to … be communicated very clearly to patients. We don’t know what we don’t know. So follow-up will be really important.”
Mitochondrial disease affects about 60 babies born in Australia every year, and many thousands of adults live with the condition, which can cause devastating illness. In 2022, Australia passed Maeve’s Law, which legalised mitochondrial donation, an IVF-based technique in which a fertilised embryo contains the genetic material of three people – the two parents, and a donor with healthy mitochondria. Although other techniques are available to minimise the risk of passing on mitochondrial disease, such as using a donor egg or embryo screening, the ability to use an IVF technique that minimises transmission but results in a child that is the genetic offspring of the parents is very important to the small number of families affected.
Joel Hood, the father of Maeve, who has Leigh syndrome, a rare, inherited neurodegenerative condition, welcomed the British births but urged some caution.
Despite Australia being a pioneer in legalising mitochondrial donation – the second country to do so after Britain – the Monash trial has been stalled for 18 months as the team struggled to gain regulatory approval to progress.
Monash IVF, the clinical partner in the trial, has had to recently inform the stock exchange of two major embryo bungles, one of which resulted in a woman giving birth to a baby that was not her biological child.
The key sticking point has been over the critical issue of whether adequate informed consent had been provided by egg donors.
Australia’s Embryo Research Licensing Committee has demanded more stringent informed consent processes specific to mitochondrial donation research.
“I’ve been trying to take a measured approach in my response to families, some having some concerns around the safety, and then others concerned about the length of time that the trial is taking,” Mr Hood said.
“We never wanted things to be done fast, with any repercussions for families. We wanted the science to be right. But I would love to see things expedited if possible, and done safely.”
Under a technique known as pronuclear transfer, nuclear DNA is extracted from an egg fertilised by two parents in which the mother is affected by a mitochondria DNA mutation, and this DNA material is transplanted to a fertilised healthy donor egg. The resulting embryo inherits its parents’ DNA, but the mitochondrial DNA is inherited primarily from the egg donor, substantially reducing the risk of the transmission of mitochondrial disease.
The director of Monash’s Biomedicine Discovery Institute and the head of mitoHOPE, John Carroll, said his team had now reached an in-principle agreement with the licensing committee, and he expected the British research would give regulatory authorities further reassurance on safety and efficacy to enable the Australian trial to proceed.
“What this paper will do is that it will provide an evidence base in which the decision-making about regulation can be made,” Professor Carroll said.
“These first indications are really very, very promising for the future. I think this should really help us to proceed and get mitochondrial donation introduced into Australia in the form of a clinical trial as soon as possible.
“It’s early days. We really have to keep just progressing with care, with caution, monitoring and reporting on all of the developments, but I think the impact of this disease on those families that are affected is profound and generational, and the opportunity or the ability to prevent future mitochondrial diseases is a really major step forward for that group.”
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