Mitochondria, a cellular power plant, contains unique special DNA that is passed on from mother to child, which can sometimes carry mutations, causing diseases that currently have no cure.
Now, in new clinical trials, it appears that eight babies at high risk of inheriting such a disease from their mothers have been spared thanks to a new technology called “mitochondrial donations.”
The approach used in this study has been in development for many years and only reaches human patients. Research co-author Mary Herbert, a professor of reproductive biology at Monash University in Melbourne, said early attempts to donate mitochondrials were first explained in a mouse experiment published in the 1980s.
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Subsequently, research into human embryos that were fertilized in vitro fertilization (IVF) but were not suitable for use was born, and instead was donated for research. Later, in 2015, the world’s first law was passed in the UK, allowing research using high-quality human embryos. Since then, scientists have improved their approach to transfer healthy mitochondria into embryos, troubleshooting many issues that have arisen along the way.
“There were hurdles at every stage,” Herbert said. Herbert has also been appointed at the University of Newcastle and the Newcastle Fartarity Centre in the UK, but the results of the trials listed in two reports published Wednesday (July 16) of the New England Journal of Medicine may provide solutions to parents who are otherwise highly likely to pass on these diseases to their children.
“That’s exactly what it takes to run through generations of women in these families,” Herbert said. “I’m really happy to be able to do something and offer some sort of way.”
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“This brought joy and relief to my parents.”
The inherited mitochondrial disease, estimated to affect approximately one in 5,000 births, can cause a wide range of symptoms, including seizures, muscle weakness, fatigue, vision loss, heart disease, developmental delays, and learning disabilities. These symptoms occur as soon as more serious presentations arise, ranging from mild and manageable to severe threats.
Although the mutations behind these diseases are known to be inherited from the mother, transfer from parent to offspring remains unpredictable. This is because in a given egg, the “mutation load” can change. Some eggs carry mitochondrial DNA with little or no harmful mutations, while others carry mitochondria with only mutated DNA.
If the affected parent is pregnant without the help of reproductive techniques, “there may be a perfectly healthy child or a child who will die in the first few days of life,” Herbert said.
When it comes to people carrying high and low-load egg mixtures, they have the option to get eggs by hand at low load using pre-transplant genetic testing (PGT), a technique combined with IVF. However, “People who are not suited for PGT are those who have a very high mutation load on all eggs, sometimes 100% mutation load,” Herbert explained.
The patient who is not necessarily extremely ill herself, but perhaps told about the mutation is a patient who can benefit from the donation of mitochondrials.
In the trial, researchers directly compared the PGT approach to mitochondrial contributions. All participants carry disease-causing mitochondrial DNA mutations, all of which are IVF, a type of IVF, a type of IVF that triggers fertilization by injecting a single sperm cell straight into the egg. Patients with low mutation loading sufficient for a portion of the egg were provided with PGT, whereas patients with too high mutation loading were provided with mitochondrial donations.
The donation itself can be made in several different ways, but in the trials researchers used “nuclear transfer.” This nucleus was removed and eggs placed in another donated egg cell were fertilized. The donated eggs have been screened for known mitochondrial mutations and have also removed their own nuclei. Therefore, the resulting embryo carries the oocyte DNA, which uses nuclear DNA from the egg institutionalized, and mitochondrial DNA from the donor egg.
Eventually, 16 of the 39 patients given PGT became pregnant and 18 babies (including twins) were born. In comparison, eight of the 22 patients who received mitochondrial donations became pregnant, resulting in the birth of eight babies so far. Both techniques resulted in a similar proportion of pregnancy out of all treated people.
“This process brought joy and relief to the parents of these children who never thought they would have had a child without the risk of mitochondrial disease,” said Dr. Bobby McFarland, professor of pediatric mitochondrial medicine and honorary consultant pediatric neurologist at Newcastle University.
“It was really special to be part of the team’s efforts to make that happen,” he told Live Science in an email.
Related: First, children treated for rare and often fatal disorders while in the uterus
More refinement of techniques
All babies pregnant through mitochondrial donations are born healthy and meet developmental milestones, the team reported.
“We are now proud of our healthy baby parents – a successful, true mitochondrial replacement,” the mother of one of the boys said in a statement. “This breakthrough lifted the heavy cloud of fear that once loomed above us.”
Children’s health continues to be monitored. “We have thrown a wide net for clinical health data on these children, including detailed developmental assessments at 18 months,” McFarland said. “We are in the process of revising our research to look for more subtle developmental issues in five years.”
In particular, the pronuclear transfer procedure does not guarantee that all the last scraps of the baby’s mitochondrial DNA are from the donor’s eggs. That’s because in the process of moving the nucleus from one egg to another, a small amount of mama’s mitochondrial DNA can be carried over with the nucleus, Herbert explained.
In the eight babies born so far, blood cells had irrelevant levels of maternal mitochondrial DNA, while other babies had detectable amounts, but the concentrations are below what is expected to cause disease. But the team will need to watch to see if the DNA carrying the mutation becomes more abundant over time, Herbert said.
“We must consider these technologies as risk reduction. We cannot guarantee prevention,” she said. Parents were informed of this restriction prior to the procedure and emphasized that they were being counselled on all options. Looking forward to it, scientists want to improve techniques to reduce the risk of bringing it in as much as possible, making the process more efficient and easier to replicate.
“Long-term surveillance of children is essential,” said Dr. Paula Amato, a professor of obstetrics and gynecology at Oregon Health & Science University (OHSU) and a former professor of the American Reproductive Association of Presidents. “But it’s reassuring that they look healthy at birth,” she told Live Science in an email. She added that she is interested in seeing how the risk of carrying over maternal DNA will be mitigated in the future.
The two groups of trial parents were different from each other, particularly in terms of mutational load, but Robin Lovellbadge, the leading group leader at the UK’s Francis Crick Institute, wrote a commentary for the New England Journal of Medicine.
“Having a group that has received PGT as a comparative group reinforces the conclusion that nuclear transfer is an effective way to reduce the risk of mtDNA. [mitochondrial DNA] He wrote illness.
Herbert says research into mitochondrial donations will continue in Australia, which passed similar regulations in the UK in 2022. McFarland added about the current trial, “This is still a relatively small number of babies and needs to be followed up longer.”
Meanwhile, in the US, the Food and Drug Administration currently does not allow clinical research into these types of “mitochondrial exchange technologies” in humans due to years of regulations passed by Congress.
“From a policy perspective, it is unfortunate that similar clinical research is not currently permitted in the United States because of FDA riders who prohibit the FDA from considering clinical trials with genetic modifications in human embryos.” Furthermore, Dickie Wicker’s revision “prohibits federal funding for research, including human embryo studies,” she said.
She noted that these restrictions are particularly unfortunate given the pioneering work done by Shoukhrat Mitalipov and other OHSU scientists. “This probably represents an opportunity for US patients to request access to these experimental therapies,” she suggested.
Editor’s Note: This story was updated on July 17, 2025 to add a comment from Dr. Paula Amato.
This article is for informational purposes only and is not intended to provide medical advice.
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