UK scientists have developed a fertilization procedure that uses the nuclear DNA of the father and the mother, but the mitchondrial DNA of a third person, an egg donor, that potentially offers couples where the mother has a family history of mitchondrial diseases, a way to have healthy children via IVF (in vitro fertilization).

You can read about how the researchers at Newcastle University in the UK developed this technique in a scientific paper published in an early online issue of the journal Nature on 14 April.

The funding for the study, which was led by led by Dr Mary Herbert and Professor Doug Turnbull, came primarily from the Muscular Dystrophy Campaign, the Medical Research Council and the Wellcome Trust.

Herbert, Turnbull and colleagues said the study is “proof of principle” that it is possible to prevent transmission of mitochondrial diseases, thus opening the door to affected mothers being able to have healthy children.

They wrote in their background information that about 1 in 200 children are born every year with mutations in their mitochondrial DNA, and in most cases this results in mild forms of mitochondrial disease, or no symptoms at all.

But for about 1 in every 6,500 children, the mutations cause severe mitochondrial diseases, including learning disability, blindness, muscular weakness, diabetes, and also fatal heart or liver failure, with death sometimes occuring in early infancy.

There are currently no treatments for mitochondrial diseases, and mothers who know they carry the mutations face difficult and agonizing decisions about whether to take the risk and try for a baby.

Each cell in our bodies has two types of DNA: nuclear and mitochondrial. Nuclear DNA contains about 23,000 genes passed on from both our parents and determines the physical and characteristic traits we inherit from them.

But mitochondrial DNA is passed on only by the mother via her egg, and this contains just a small number of genes, about 13, that control each cell’s mitochondria , the tiny “power plants” that generate the energy used by the cell.

So to find out it if it is possible to avoid disease-causing mutations in mitochondrial DNA from passing from mother to child, the researchers started looking at the possibility of replacing the mitochondrial DNA of an egg fertilized via IVF with non-mutated mitochondrial DNA from a donated egg.

They eventually succeeded, for the first time in human fertilized eggs, in removing the “pronuclei” of fertilized eggs (the nucleus of the sperm and the nucleus of the egg after the sperm has entered the egg but just before they fuse), leaving behind the mutated mitochondrial DNA, and placing the extracted pronuclei into donor eggs whose pronuclei had been removed but whose mitochondrial DNA did not have disease-carrying mutations.

The result is fertilized human eggs with nuclear DNA from the father and the mother and the mitochondrial DNA of the donor.

To explain the process, Turnbull, likened it to replacing the battery on a laptop computer:

“The energy supply now works properly, but none of the information on the hard drive has been changed,” said Turnbull.

“A child born using this method would have correctly functioning mitochondria, but in every other respect would get all their genetic information from their father and mother,” he stressed.

Turnbull said this was an exciting development with “immense potential to help families at risk from mitochondrial diseases”.

“We have no way of curing these diseases at the moment, but this technique could allow us to prevent the diseases occurring in the first place. It is important that we do all we can to help these families and give them the chance to have healthy children, something most of us take for granted,” he urged.

For the study, Herbert, Turnbull and colleagues fertilized 80 eggs and cultured them for up to 8 days in the lab, until they reached the blastocyst stage (when they have about 100 cells). In the UK, this process is strictly controlled by licensing criteria set by the Human Fertility and Embryology Authority (HFEA) in 2005.

The donor eggs came from couples going through IVF treatment at the Newcastle Fertility Centre at Life. Sometimes fertility treatment results in eggs that are fertilized but not suitable for IVF. The egg donation and ethical part of the study was conducted under the supervision of co-author Professor Alison Murdoch.

The researchers said that in some of the eggs, a small amount of mitochondrial DNA passed from the mother to the new egg, but since severe mitochondrial diseases only develop when a lot of mutations pass across, they concluded this was unlikely to pose a high risk to a child’s health.

They are now planning to do more research on the safety of the procedure. Although the revision made to the Human Fertility and Embryology (HFE) Act in 2009 currently forbids fertility treatments via this method, it includes a provision for Secretary of State for Health to make it permissible in the future.

“Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease.”
Lyndsey Craven, Helen A. Tuppen, Gareth D. Greggains, Stephen J. Harbottle, Julie L. Murphy, Lynsey M. Cree, Alison P. Murdoch, Patrick F. Chinnery, Robert W. Taylor, Robert N. Lightowlers, Mary Herbert and Douglass M. Turnbull.
Nature, advance online publication 14 April 2010

Source: Newcastle University.

Written by: Catharine Paddock, PhD