U.S. study identifies challenge for 3-parent IVF's effectiveness

A U.S. study released Thursday reported a potential hurdle to the effectiveness of a technique that aims to prevent certain genetic diseases but would create babies with genetic materials from three parents.

Mitochondrial replacement therapy, also known as "three-parent in vitro fertilization (IVF)," involves replacing the faulty mitochondria in a mother's eggs with healthy mitochondria from another woman.

Such a treatment could help prevent the inheritance of mitochondrial DNA diseases that can result in serious health problems including developmental delay and premature death, but the resulting embryo contains genetic material from three people: the parents and an egg donor.

Mitochondrial replacement therapy has been approved in the United Kingdom, and the U.S. National Academies of Sciences, Engineering, and Medicine recently concluded it is ethically permissible to conduct clinical investigations in the United States.

However, the new study, published in the U.S. journal Cell Stem Cell, found that small amounts of mitochondrial DNA can sometimes hitch a ride with the transferred nucleus and that this DNA can override the mitochondria in the donor cell.

"We identified a challenge to making mitochondrial replacement therapy safe and effective," said senior study author Dieter Egli of the New York Stem Cell Foundation.

"We anticipate that the findings will inform decisions regarding when and how mitochondrial replacement in humans will be done clinically," Egli said.

Using healthy human egg cells, Egli and his collaborators transferred the nuclear genome of an "original" egg cell into an unfertilized "donated" egg cell.

Half of the resulting cells contained a low percentage of mitochondrial DNA from the original egg cell, not just the donated egg cell, they found.

The transferred mitochondrial DNA vanished over time in most cases, showing that complete mitochondrial DNA replacement is possible, the researchers said.

But what's surprising was that a few of the cells underwent complete reversion, with up to 100 percent of the mitochondrial DNA matching that of the transferred DNA.

Eric Shoubridge, principal investigator at McGill University's departments of human Genetics and neurology and neurosurgery, who was not involved in the study, said in a statement: "The implications for the clinic are simply that one should proceed with caution."

Shoubridge noted that further studies are required in developing zygotes post-fertilization to see whether mitochondrial DNA carryover is a problem in the actual embryo. Endit