Human embryo repair experiment swaps out faulty mitochondrial DNA

A new therapeutic technology to prevent women from passing on debilitating disorders to their babies has worked successfully in a small, proof-of-concept experiment.

Mitochondrial replacement therapy, colloquially known as the three-parent baby procedure, is designed to prevent diseases rooted in bad or mutant DNA in the mitochondria.

Mitochondria are the power plants or batteries in our cells that provide energy. When there are defects in mitochondrial DNA, progressive diseases can result that affect our energy-intensive organs, such as the brain, heart, muscles and liver.

"Currently there are no cures, and these diseases can be debilitating and often fatal," Paula Amato of Oregon Health & Science University told reporters.

• Genetically modified baby born with DNA from 2 women
• Why Canada isn't ready to talk about '3-parent' babies

Since we only inherit mitochondrial DNA from our mothers, it's hoped that swapping out these DNA mutations from the mitochondria in human eggs or ova will prevent defects in the baby.

In vitro replacement

Amato, Shoukhrat Mitalipov and their team published an early-stage study in the journal Nature this week describing how they used a technique to replace faulty mitochondria with those from a healthy donor egg stripped of its nucleus. 

"What they're doing here is essentially a form of in vitro fertilization where they're trying to get rid of the bad mitochondrial DNA," said Dr. Mark Tarnopolsky, a clinician and scientist at McMaster University's pediatrics department who studies mitochondrial diseases. He wasn't involved in the study.

The therapy is designed so that the mother's healthy nuclear DNA is still passed on while the mitochondrial DNA comes from a donor egg.

"What you have is this hybrid or fusion type of an egg," Tarnopolsky said. "You've got this nucleus now that contains all of that healthy, good genetic material in the nucleus from the original mom who had mitochondrial disease. Now that mom has a hybrid egg, which has nice, fresh mitochondria from the donor mom."

Until now, published research into mitochondrial DNA in humans used eggs with normal, not diseased mitochondrial DNA.

The investigators replaced the mitochondria, fertilized the hybrid egg, and produced healthy embryos to the blastocyst stage. That's when fertility clinics normally implant the embryo in a woman's uterus.

The diseases themselves are rare, affecting an estimated one in 5,000 children worldwide, Tarnopolsky said.

Donor match considered

In rare instances in the experiment, Amato and Mitalipov's team found some defective mitochondria still contaminated the fertilized embryos.

Mitalipov suggests choosing egg donors with closely matched mitochondrial DNA to overcome the issue. He didn't think it would slow clinical trials, in up to 15 families, if U.S. regulators approve it.  

"What we have to do is to be as careful as we can to try and match the donor mitochondrial DNA," said Eric Shoubridge at the department of human genetics at McGill University in Montreal, who wrote a journal commentary that accompanies the study.

"We want them to be essentially on a similar mitochondrial DNA background so they're going to replicate at the same rate. So even if the mom who is carrying the mutations [has] a few of her mutations get carried over, it's not going to outmanoeuvre, if you will, the ones from the donor egg."

The procedure is complex and not many clinics worldwide are licensed to do it, Shoubridge said.

This week in Britain, a panel advising the U.K. fertility regulator recommended the techniques now be approved for "cautious" use in "specific circumstances."

Baby born using technique

Earlier this year, U.S. doctors working at a clinic in Mexico helped a Jordanian couple to conceive a baby from a genetically modified embryo with DNA from its mother, father and a female mitochondrial DNA donor using a similar technique.

Nothing has been published about the baby boy in the scientific literature yet, Shoubridge said.

He said many of those working in the area would like to see any births occur under the carefully controlled conditions of a clinical trial. That way, rules are in place to make it as safe as possible.

In all cases, doctors need to follow the children closely as they grow, Tarnopolsky said.

The procedure is currently illegal in Canada.

"I think it should be something that in Canada we should offer at some point," Shoubridge said.