Could mitochondrial replacement help treat some genetic diseases?

Mitochondrial DNA (mtDNA) includes 37 genes and is directly inherited from a person's mother. Mitochondrial disorders occur when there are mutations in these genes and can cause serious health problems, such as paralysis, heart failure, brain damage, stroke, and blindness. Currently, one in 5,000 children has a mitochondrial disorder.

In the study, British researchers tested a new treatment for these disorders called mitochondrial replacement therapy or mitochondrial donation. Through a method called pronuclear transfer, the researchers removed two pronuclei from an egg cell in the early stages of fertilization and inserted them into a donor egg cell that had its own nucleus removed. This resulted in a fertilized egg with nuclear DNA from the original parents and healthy mitochondria provided by a donor.

Overall, 22 women with pathogenic mtDNA variants underwent in vitro fertilization (IVF) and received mitochondrial replacement therapy. In total, there were eight live births, and one pregnancy is still ongoing.

Of the eight babies, none of them had signs of mtDNA disease. Levels of maternal pathogenic mtDNA variants were 95% to 100% lower in six of the babies and 77% to 88% lower in two of the babies compared to corresponding zygotes that had their nuclei removed. Heteroplasmy levels in the children's blood also ranged from undetectable to 16%.

Commentary

Dietrich Egli, an associate professor of developmental cell biology at Columbia University, called the research "a landmark advance" and "pioneering work."

"It is extraordinary — no question about it," Egli added.

"Mitochondrial disease can be devastating for the family. It can be tragic," said Doug Turnbull, a professor of neurology at Newcastle University and one of the study's authors. "This is an important breakthrough — a big step forward."

However, even with positive results, some researchers have spoken out against the treatment, saying that mistakes could introduce dangerous mutations into the human gene pool and that it could potentially lead to people manipulating genes to create "designer babies."

"It's dangerous," said Stuart Newman, a professor of cell biology and anatomy at the New York Medical College. "It's biologically dangerous. And then it's dangerous culturally because it's the beginning of biological manipulation that won't just end with preventing certain diseases, but will blossom into a full-fledged eugenics program where genes will be manipulated to make designer babies."

"There are risks to the women who are going to be receiving the embryo and there are risks to the women who are the donor of the eggs that will be providing the mitochondria," said Francois Baylis, a distinguished research professor emerita at Dalhousie University in Canada. "We don't know the future."

The procedure has been banned in the United States since 2015 since it alters the DNA of embryos in a way that can be inherited. So far, the procedure has only been performed in a few other countries, including Mexico, Greece, Ukraine, and Cyprus.

The United Kingdom was the first country to specifically authorize the procedure, and Australia legalized the treatment in 2022. In both countries, the treatment can only be used to prevent serious mitochondrial disease.

According to Turnbull, reproductive technologies are highly regulated in Britain and many other countries, reducing potential risks. "I think there are enough checks and balances in the system to prevent this from becoming a slippery slope to designer babies," he said.

Other researchers also noted that mitochondrial replacement is distinct from gene-editing techniques like CRISPR, which have also led to concerns about designer babies.

"This is totally different," said Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute in London. "This is using a method that is avoiding a serious disease. If you care about [people's] health, [people's] desire to have genetically related children, then I see no reason why you should not accept these methods."