The Human Fertilisation and Embryology Authority (HFEA) has granted permission for doctors to create the UK's first 'three-person' children by mitochondrial donation.

Doctors at Newcastle Fertility Centre successfully applied to treat two women and are now allowed to create embryos by combining fertilised eggs created through IVF with mitochondria from a female donor. The resulting embryos will be implanted in the two women.

Mitochondrial donation was developed for use where women carry disease-causing genetic mutations in their mitochondria. Mitochondria are small structures located in the cell which produce energy and also house their own distinct DNA, separate from the main bulk of DNA located in the cell nucleus.

To avoid passing on these mutations to their children, the healthy nuclear DNA of the intended parents is removed from a fertilised egg and transplanted into the fertilised egg of a female donor whose nuclear material has been removed, resulting in an embryo with nuclear DNA from two parents and the mitochondrial DNA of the donor. An alternative method involves performing the DNA transfer before fertilisation.

The decision by the HFEA has already been warmly welcomed by UK advocacy groups. Liz Curtis, founder of the British mitochondrial disease charity The Lily Foundation, said: 'The first patient licence for mitochondrial donation has been a long time coming, but now at last women with mitochondrial disease have a chance to have children without fear of passing on this devastating condition.'

In both of the currently approved cases, the women carry a genetic mutation for a condition called MERRF syndrome. The disease is characterised by twitching, weakness and progressive tightness in the muscle fibres. This can lead to symptoms such as difficulty coordinating movement, seizures and heart disease.

Professor Salvatore DiMauro, an expert in mitochondrial disease at Columbia University in New York, said: 'It's good to do this. MERRF is a crippling disease. It's the only way to be sure it is not passed on.'

Newcastle Fertility Centre, which has pioneered much of the research in this field, received a licence to perform mitochondrial donation techniques last March from the HFEA, but it has taken nearly a year for these two specific cases to be approved. 

Responding to the news, Sarah Norcross, Director of the Progress Educational Trust, said: 'The pace at which these treatments are being rolled out may seem slow, but this highly regulated and measured approach will ensure the highest standards of treatment and follow-up research. Options which for many years have been tantalisingly out of reach to patients are now a step closer.'

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Ke-Hui Cui   13 April 2018
MRT WILL DAMAGE CENTROSOME AND NATURAL GENETIC SCREENING SYSTEMS FOR HEREDITY
MRT WILL DAMAGE CENTROSOME AND NATURAL GENETIC SCREENING SYSTEMS FOR HEREDITY The centrosomes are the command centers for cellular control, in cell division (cytokinesis) and also in cell-cycle progression. Recently, identification of many kinds of RNA and more than three hundreds of proteins in and around centrosome has highlighted the evolutionary conservation of centrosome functions. The centrosome not only serves as the microtubule-organizing centers (MTOC) but also as the actin organizing center, the intermediate filament organizing center and the Golgi organizing center. Any change on the centrosomes can block or impede the division, because its function to organize the astral microtubules to further orient spindle are damaged (with defects in microtubule furrows). Heredity in one species is very stable. Human beings have a history about five million years with countless times of cell division, and still have a karyotyping of 46 chromosomes. Some aneuploidy cells are producing all the time, in embryos, fetuses, children to every one of us. Why are most people not to be aneuploidy or mosaicism? The reason is: The eukaryote cells contain several families of protein kinases such as cyclin-dependent kinases (Cdks), polo-like kinases (Plks), Aurora family of kinases, and many other families of proteins to form natural genetic screening systems. The systems include checkpoints and licensing factors for DNA replication, for centrosome duplication and for spindle assembly. Cycle of centrosome duplication and cycle of DNA replication are coordinating, or in parallel. Problems in such coordination are commonly seen in many aneuploidy and cancers. In the coordination of these two cycles, a lot of proteins in cytoplasm and centrosome play as regulation functions. One of the centrosomal substrates, cdk2 couples centriole duplication to the onset of DNA replication at the G1/S phase transition. The similar G1/S phase regulating proteins include cyclins D and E, cdk4 and 6, cdk inhibitors p53, ZYG-1, Aurora kinases, … etc. They regulate the G1 phase to be finished perfectly before progress into S phase. Or else, the cells will arrest in G1 phase. Plks are important mediators for various cell cycle checkpoints that monitor centrosome duplication, DNA replication, segregation of chromosomes, and mitotic exit. Without mitotic exit, the abnormal cell, such as aneuploidy cells, cannot divide. Apoptosis will happen in these cells later, and normal cells will continuously grow and divide. Some aneuploidy cells produced in cell growing courses are physiological rather than pathological. That means: it is not an illness. When the natural genetic screening system is damaged or the immune system is also damaged, pathological entity such as the aneuploidy or cancer will happen. The natural genetic screening system is very strict. Any cell to be divided should pass the above three kinds of checkpoints and licensing systems under further regulation – up to at least 10 to over 30 times of examinations. If in the embryos of in vitro fertilization (IVF), this system in the cells may be called natural preimplantation genetic screening (PGS). The natural PGS functions much stronger than the artificial PGS for elective single embryo transfer (eSET) performed in some IVF clinics. It allows only about 1% live birth to be abnormalities, and true fetal mosaicism to be less than 0.5%. It also avoid the embryo cytoskeletons being damaged by repeated temperature change and by invasive techniques, which were usually with artifact results. The damaged cytoskeleton by artificial PGS influenced normal neuron growth and mental development in mice experiments and human clinical results. When SCNT and MRT were performed, the natural PGS system of the normal cell heredity was thoroughly damaged by spindle extraction. Ke-Hui Cui