The mitochondrial replacement therapy (mitochondrial replacement therapy, or MRT) is an innovative reproductive technology aimed at preventing the transmission of mitochondrial diseases from mother to child.

The mitochondria they are organelles contained within our cells that produce energy. They contain 37 stamina cells, less than 0,1 % of the genetic material of our species, the vast majority of which is found within the nucleus of our cells.

How the MRT works

When mutations occur in mitochondrial DNA, these can lead to the inheritance of serious neurodegenerative diseases, currently without treatment, which mainly affect tissues with high energy expenditure, like heart, brain and muscles. In total, there are more 200 different shapes, with a incidence of about 1 are 5.000 born alive.

The mitochondrial replacement procedure involves several steps: the transfer of nuclear genetic material from an egg of a woman who has a mitochondrial disease to an egg that has had its nuclear genetic material removed. Then this egg containing genetic material from two women is fertilized with sperm from the future father. The resulting fertilized egg has a complete set of chromosomes from both parents, but carries the donor's healthy mitochondria. Subsequently, this egg is implanted in the uterus of the future mother.

Mitochondrial DNA vs nuclear DNA

This year United Kingdom was the first country to approve the clinical use of MRT more than 9 Years ago, in February 2015. Approval for this type of technology is granted on a case-by-case basis by the Human Fertilization and Embryology Authority (Human Fertilisation and Embryology Authority, HFEA) of the United Kingdom, which gave the green light for at least 30 almost. This marked a significant milestone in the field of reproductive medicine.

Australia has become in 2022 the second country to give approval to the MRT. However, the procedure remains limited in many other countries, including the United States. The procedure has also been performed in other countries, where, however, its use is not regulated. In 2016, A US doctor announced he successfully used MRT to prevent mitochondrial disease in a child in a procedure conducted in Mexico. Babies have also been born through mitochondrial transfers conducted in Greece and Ukraine. In response to a Guardian inquiry in April 2023, the Authority for Human Fertilization and Embryology (HFEA), the fertility regulator in the UK, confirmed that fewer than five babies were born in the UK using this procedure.

The widespread debate about this technology in the United Kingdom initially focused on the fact that the child brought into the world with this technology has genetic material from three donors (the technology was also nicknamed in English “3-parent-baby”). After this was resolved in a pragmatic way, as the English usually do, considering the genetic contribution of mitochondria irrelevant for the development of the child's identity, the debate has therefore moved on (and stays centered) on the costs and sustainability of the technology by the national health system, when there are alternatives, even if not optimal, Alla MRT.

What are these alternatives? Women with mitochondrial mutations can avoid passing on the mutations by adopting a baby boy or girl, or they can have a child not genetically related to them by undergoing in vitro fertilization (IVF) heterologous (not in Italy). Or, to have genetically related children, Affected women can undergo embryo screening for mitochondrial mutations through preimplantation diagnosis in the context of medically assisted reproduction. Although effective in many cases, preimplantation diagnosis reduces the risk rather than eliminating it completely, and it can't help when all the embryos produced by a woman have highly mutated mitochondria.