First UK Baby With DNA From Three People Born After New IVF Procedure


 
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By Ian Sample

The first UK baby created with DNA from three people has been born after doctors performed a groundbreaking IVF procedure that aims to prevent children from inheriting incurable diseases.

The technique, known as mitochondrial donation treatment (MDT), uses tissue from the eggs of healthy female donors to create IVF embryos that are free from harmful mutations their mothers carry and are likely to pass on to their children.

Because the embryos combine sperm and egg from the biological parents with tiny battery-like structures called mitochondria from the donor’s egg, the resulting baby has DNA from the mother and father as usual, plus a small amount of genetic material – about 37 genes – from the donor.

The process has led to the phrase “three-parent babies”, though more than 99.8% of the DNA in the babies comes from the mother and father.

Research on MDT, which is also known as mitochondrial replacement therapy (MRT), was pioneered in the UK by doctors at the Newcastle Fertility Centre. The work aimed to help women with mutated mitochondria to have babies without the risk of passing on genetic disorders. People inherit all their mitochondria from their mother, so harmful mutations in the “batteries” can affect all of the children a woman has.

For affected women, natural conception is often a gamble. Some babies might be born healthy because they inherit only a tiny proportion of the mutated mitochondria. But others may inherit far more and develop severe, progressive and often fatal diseases. About one in 6,000 babies are affected by mitochondrial disorders.

Most of a human’s 20,000 genes are coiled up in the nucleus of nearly every cell in the body. But dotted around each nucleus are thousands of mitochondria with their own genes. When functioning properly, the mitochondria provide vital energy for the cells that make up our organs. Mutations that damage the mitochondria tend to affect energy-hungry tissues most: the brain, heart, muscles, and liver. These can deteriorate relentlessly as an affected child grows.

Progress with MDT led parliament to change the law in 2015 to permit the procedure. Two years later, the Newcastle clinic became the first and only national centre licensed to perform it, with the first cases approved in 2018. Approval is given on a case-by-case basis by the UK’s Human Fertilisation and Embryology Authority (HFEA), which has given the green light for at least 30 cases.

Doctors at the Newcastle clinic have not released details of births from its MDT programme, amid concerns that specific information could compromise patient confidentiality. But in response to a freedom of information request, the HFEA confirmed that a small number of babies have now been born in the UK after MDT.

The regulator said the number of births was “less than five” rather than giving the precise figure, because doing so “could lead to the identification of a person to whom the HFEA owes a duty of confidentiality”. The number was accurate as of late April 2023, it said. No further details of the births were provided.

The treatment programme was substantially delayed by the pandemic, which deterred some donors from coming forwards and affected couples hoping to go ahead with the therapy.

The Newcastle process has several steps. First, sperm from the father is used to fertilise eggs from the affected mother and a healthy female donor. The nuclear genetic material from the donor’s egg is then removed and replaced with that from the couple’s fertilised egg. The resulting egg has a full set of chromosomes from both parents, but carries the donor’s healthy mitochondria instead of the mother’s faulty ones. This is then implanted in the womb.

The procedure is not without risks. Recent research has found that in some cases, the tiny number of abnormal mitochondria that are inevitably carried over from the mother’s egg to the donor egg can multiply when the baby is in the womb. So-called reversion or reversal could lead to a disease in the child. “The reason why reversal is seen in the cells of some children born following MRT procedures, but not in others, is not fully understood,” said Dagan Wells, a professor of reproductive genetics at the University of Oxford who took part in the research.

Women with mitochondrial mutations can avoid passing on disorders by adopting or having IVF with a donor egg. Or, to have genetically related children, affected women can have their IVF embryos screened for mitochondrial mutations. Though effective in many cases, this reduces the risk rather than removing it completely, and it cannot help when all of the embryos a woman produces have highly mutated mitochondria.

The UK is not the first country to create babies from MDT. In 2016, a US doctor announced the world’s first MDT birth after treating a Jordanian woman who carried mitochondrial mutations that cause a fatal condition called Leigh syndrome. Prior to the treatment, performed in Mexico, the woman had four miscarriages and two children. One died aged six, the other lived for only eight months.

“So far, the clinical experience with MRT has been encouraging, but the number of reported cases is far too small to draw any definitive conclusions about the safety or efficacy,” said Wells. “Long-term follow-up of the children born is essential. The stage of development when reversal happens is unclear, but it probably occurs at a very early stage. This means that prenatal testing, carried out [at] about 12 weeks of pregnancy, may well succeed in identifying if reversal has occurred.”

Sarah Norcross, the director of Pet, a charity that improves choices for people affected by infertility and genetic conditions, said it was important for the technology to be used in a “measured and carefully regulated way” while it is assessed. “It is also very important that we respect the privacy of children with donated mitochondria, and their parents, not least because these parents are likely to have had prior experience of illness and bereavement in their family,” she added.

Peter Thompson, chief executive at the HFEA, said: “MDT offers families with severe inherited mitochondrial illness the possibility of a healthy child. The UK was the first country in the world to allow MDT within a regulatory environment … These are still early days for MDT and the HFEA continues to review clinical and scientific developments.”

A spokesperson for Newcastle Hospitals NHS Foundation Trust and Newcastle University said: “Academic publications have been submitted and are going through the process of scientific peer review. This means we are unable to comment further at this time in order to avoid prejudicing the process.”


 
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