Spindle transfer

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 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. 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 (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 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. 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; it could only be performed in clinics licensed by the UK's Human Fertilisation and Embryology Authority (HFEA), only for people individually approved 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.:45 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/organ transplantation. In in vitro fertilization and involves removing eggs from a woman, removing sperm from a man, fertilizing the egg with the sperm, allowing the fertilized egg to form a blastocyst, and then implanting the blastocyst. MRT involves an additional egg from a third person, and manipulating both the recipient egg and the donor egg. As of 2016 there were three MRT techniques: maternal spindle transfer (MST), pronuclear transfer (PNT), and more recently as of that date, polar body transfer (PBT). The original technique, in which cytoplasm taken from a donor egg and containing mitochondria, is simply injected into the recipient egg, is no longer used.:46–47 In MST, an oocyte is removed from the recipient, and when it is in the metaphase II stage of cell division, the spindle-chromosome complex is removed; some of cytoplasm comes with it, so some mitochondria are likely included. The spindle-chromosome complex is inserted into a donor oocyte from which the nucleus has already been removed. This egg is fertilized with sperm, and allowed to form a blastocyst, which can then be investigated with preimplantation genetic diagnosis to check for mitochondrial mutations, prior to being implanted in the recipient's uterus.:47–48