In the UK, eight babies were born that were created by special artificial fertilization. Inheritance material was combined for the first time by three people: Kern DNA from a maternal egg cell and a fatherly sperm and DNA from mitochondria of a donated egg cell. This procedure is intended to protect the babies from diseases that are inherited through the maternal mitochondrial DNA. The first tests now show that this has succeeded and that the babies have so far been healthy. However, the mitochondria replacement therapy is still not absolutely safe and the risk that small amounts of the mutated mitochondria DNA will also be transmitted to the mother. It is unclear whether the method would be permitted in Germany.
Our genetic material is mainly in the core of our cells. This core DNA contains all genes that make up a person, including its appearance and character. In addition, the mitochondria also have small DNA molecules that contain special genetic information for the energy balance of the cell. It is only a few dozen genes. However, mutations in this mitochondrial DNA (MTDNA) can cause serious hereditary diseases. For example, the heart, muscles or brain can be supplied with too little energy, which can lead to disabilities or even death. This affects one of 5,000 children who are born annually. Since the mitochondrial DNA is only inherited from the mother, men can also develop such inherited diseases. But only women can also pass on to their descendants. For years, researchers have been looking for paths to treat these genetic defects safely and reliably, but so far without success.
Transfer of the parental DNA into donor ice cream
Researchers around Louise Hyslop and Robert McFarland from Newcastle Fertility Center have developed a method in Great Britain that can prevent inheritance of such mutations. It is a special technique for artificial fertilization (IVF), in which genetic material is combined by three people. For this, a healthy woman initially donates an egg cell, from which the so-called pre-core DNA is then removed, but mitochondria remain in the egg cell. At the same time, an egg cell of the later mother is artificially fertilized, so that it includes maternal and fatherly pre-core DNA. Then both pre-seeds of these fertilized egg cell are removed and transferred to the gutted donor ice cream. A few days later, this is inserted into the mother’s uterus. The developing embryo contains the core DNA of its two parents and the mitochondrial DNA of a healthy foreign donor. He is therefore genetically related to his parents, but has a significantly lower risk of an MTDNA disease.
This procedure of the “Pronuclear Transfer” has been legally approved in the UK since 2015 and under regulated conditions in individual cases. Since then, the researchers have offered this mitochondria replacement therapy selected women who suffer from a mitochondrial hereditary disease and accompanies them during and after pregnancy. Now seven of the women have born a total of eight babies that were generated with this IVF technology: four girls and eight boys, including an identical twin couple. All eight babies were healthy at birth, developed normally in the 18 months and show no signs of her mother’s mitochondrial hereditary disease, as Hyslop, McFarland and her colleagues report. Generysis of the babies of the blood and urine samples confirmed that their mitochondria either do not wear any disease-causing mutations or only occur in a maximum of 20 percent of their mitochondria. In order for the disease to break out, at least 80 percent would be necessary, as the team explains.
Contamination not excluded from DNA transfer
The researchers conclude that the pronuclear transfer was successful with these babies. When transferring the pre-cores from the fertilized cell, core DNA was therefore almost exclusively transferred and hardly or no mitochondrial DNA. In this way, it was possible to prevent the embryos from inheriting their mother’s hereditary disease. “Mitochondrial diseases can have devastating effects on families,” says co-author Douglass Turnbull from Newcastle University. “Today’s message gives many other women new hope of running the risk of inheriting their illness. They now have the chance to get children who grow up without this terrible illness.”
The team now wants to optimize its transfer method in order to further reduce the risk of contamination with maternal mitochondrial DNA. “The results give rise to optimism. In order to further improve the treatment results and better understand the limits of mitochondrial donor technologies, further research will be essential,” says senior author Mary Herbert from Newcastle University. The children already born should also be accompanied and examined up to the age of five in order to identify possible side effects or late consequences of the IVF method and to assess their security in the long term.
Application also in Germany?
It is still unclear whether such a mitochondria replacement would also be possible in Germany. “The German Embryo Protection Act prohibits a targeted germination line, even if it is carried out to prevent an inherited disease. But whether in the event of the exchange of mitochondria there is actually a forbidden germination intervention intervention is very controversial among lawyers,” explains right -wing expert Jochen Taupitz from the University of Mannheim. Egg cells are clearly protected by the law and are therefore inviolable. “But whether the isolated pre -kernels of an egg cell, which are to be implanted into another egg cover with non -defective mitochondria, are still as a human ‘cell’ and thus as suitable crime objects is controversial. The same applies to the stuck egg cover in which the pre -kernels are implanted,” says Taupitz. Because the change in nuclear cells and their genetic makeup is punishable, but the pure exchange of the genetic information could not be.
However, it is probably also prohibited by law to use a donor iron. Firstly, because this is also fertilized during the procedure. In this way, an embryo is legally created, which is then abused to only use the cell cover and mitochondria. On the other hand, because the donation of an egg cell alone is not allowed in Germany. In addition to the egg nucleus and inheritance, this ban could also include the remaining components. The laws aim to prevent “designer babies”. It is unclear whether a baby with exchanged mitochondria also applies as such. Before women in Germany can use the transfer method, these questions must be clarified in court.
What alternatives have women with mitochondria defect?
In addition to the pronuclear transfer, there is also an alternative for women with MTDNA-based diseases. You can have one of your own untreated egg cells fertilized and have the embryos examined for the genetic defect before planting in the uterus. This pre -implantation diagnosis is allowed in Germany with high disease risks. However, it is only promising if the triggering mutation only occurs in a small part of the mitochondria and thus only in some egg cells and not in all or most, as the researchers explain. Therefore, doctors only carry them out if the risk of illness is manageable.
Another alternative to mitochondria replacement therapy and even safer with a view to the hereditary disease would be to fertilize and use an egg cell of a healthy donor-at least in the UK, where this is allowed. Then the baby would not be genetically with the mother who held the child, but was related to the egg donor and father.
Sources: Louise Hyslop (Newcastle Hospitals NHS Foundation Trust) et al.; New England Journal of Medicine, Doi: 10.1056/nejmoa2415539 / Robert McFarland (Newcastle Hospitals NHS Foundation Trust) et al.; New England Journal of Medicine, Doi: 10.1056/Nejmoa2503658
