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Mitochondrial replacement therapy

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Mitochondrial replacement therapy

Mitochondrial replacement therapy (MRT), sometimes called mitochondrial donation, is the replacement of mitochondria in one or more cells to prevent or ameliorate disease. MRT originated as a special form of in vitro fertilisation in which some or all of the future baby's mitochondrial DNA (mtDNA) comes from a third party. This technique is used in cases when mothers carry genes for mitochondrial diseases. The therapy is approved for use in the United Kingdom and Australia. Eight babies have been born using MRT in the UK as of July 2025. A second application is to use autologous mitochondria to replace mitochondria in damaged tissue to restore the tissue to a functional state. This has been used in clinical research in the United States to treat cardiac-compromised newborns.

Mitochondrial replacement therapy has been used to prevent the transmission of mitochondrial diseases from mother to child In the UK it could only be performed in clinics licensed by the Human Fertilisation and Embryology Authority (HFEA), only for people individually approved by the HFEA, for whom preimplantation genetic diagnosis is unlikely to be helpful, and only with informed consent that the risks and benefits are not well understood.

Relevant mutations are found in about 0.5% of the population and disease affects around one in 5000 individuals (0.02%)—the percentage of people affected is much smaller because cells contain many mitochondria, only some of which carry mutations, and the number of mutated mitochondria need to reach a threshold in order to affect the entire cell, and many cells need to be affected for the person to show disease.

The average number of births per year among women at risk for transmitting mtDNA disease is estimated to approximately 150 in the United Kingdom and 800 in the United States.

Prior to the development of MRT, and in places where it is not legal or feasible, the reproductive options for women who are at risk for transmitting mtDNA disease and who want to prevent transmission were using an egg from another woman, adoption, or childlessness.

Autologous mitochondria extracted from healthy tissue and supplied to damaged tissue has been used to treat cardiac-compromised newborns. Alternatives to the approach include use of an extracorporeal membrane oxygenator (ECMO) or tissue or organ transplantation.

In vitro fertilization involves removing eggs from a woman, collecting sperm from a man, fertilizing the egg with the sperm, allowing the fertilized egg to form a blastocyst, and then transferring the blastocyst into the uterus. MRT involves an additional egg from a third person, and manipulation of both the recipient egg and the donor egg.

As of 2016 there were three MRT techniques in use: maternal spindle transfer (MST); pronuclear transfer (PNT); and the newest technique, polar body transfer (PBT). The original technique, cyroplastic transfer, in which mitochondria-containing cytoplasm taken from a donor egg is simply injected into the recipient egg, is no longer used. The UK Parliament only approved the use of two techniques -maternal spindle transfer and pronuclear transfer - for mitichondrial replacement in 2015.

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