Scientists cleared away remaining safety hurdles to recommend “cautious adoption” of mitochondrial replacement therapy for devastating inherited diseases.
Babies born after the treatment would effectively have three genetic parents. A tiny proportion of their DNA would come from their mother, father and a third person, an egg donor.
The aim is to replace abnormal genes in the mitochondria, rod-like power plants in cells that generate energy.
Following the fourth and last report from the expert panel it is highly likely Britain’s fertility regulator the Human Fertilisation and Embryology Authority (HFEA) will now give the go-ahead in principle for mitochondrial replacement to enter the clinic.
The HFEA will consider the issue at a pivotal meeting on December 15, when it will decide whether clinics may make applications to offer the treatment.
If it agrees with the scientists, the first women - probably no more than a few - could undergo mitochondrial replacement therapy as early as March or April next year.
The trail-blazing mothers undergoing the untried procedure would be acting as guinea pigs whose experiences will be written up in scientific journals.
Scientists at the University of Newcastle, which pioneered mitochondrial replacement, are poised to submit an application to the HFEA, it is understood. The regulator will look at applications on a patient-by-patient basis.
Dr Andrew Greenfield, who chaired the expert panel and is an HFEA board member, said: “We think that the cautious approach to the use of mitochondrial donation in treatment that we recommend strikes the right balance between offering access to this exciting new treatment to couples at real risk of having a genetically-related child with mitochondrial disease, while doing all we can to ensure that the treatment is safe and effective.”
Mitochondria only hold around 0.1% of a person’s DNA, which is always inherited from the mother and has no influence over individual characteristics such as appearance and personality. It is quite separate from the DNA in the cell nucleus which house the vast majority of an individual’s genes.
But when mitochondrial DNA (mtDNA) goes wrong the results can be catastrophic, leading to a wide range of potentially fatal conditions affecting vital organs, muscles, vision, growth and mental ability.
Mitochondrial replacement, conducted by fertility doctors, involves removing faulty mitochondria and substituting healthy versions from a donor.
It is carried out by transferring the genetic material that effectively encodes a baby’s identity to a donor egg whose own nuclear DNA has been removed. Two different techniques may be employed, either before or after fertilisation.
The end result is the same - an embryo containing healthy mitochondria from the donor and nuclear DNA from the baby’s mother and father.
In theory mitochondrial replacement can not only prevent a child developing inherited diseases, but also protect future generations.
Last year the UK became the first country in the world to legalise mitochondrial replacement after MPs and peers voted in favour of allowing it.
A key point considered by the expert panel was whether mitochondrial replacement had any advantage over pre-implantation genetic diagnosis (PGD). This technique is used to screen IVF embryos for genetic defects so that only healthy ones are selected for transfer into a mother’s womb.
But even with PGD a certain amount of abnormal mtDNA can slip through. For women with high levels of abnormal mtDNA, the procedure was not an option, the panel decided.
The scientists said PGD might be appropriate for less affected women, but would always be no more than a “risk reduction strategy”.
They also looked at the chances of disease-causing DNA side-stepping mitochondrial treatment. Research had shown that small amounts of mtDNA, below 2%, could be “carried over” and end up in the donor egg.
This was too small an amount to cause any problems. But stem cell experiments showed that in a few cases the carried-over mtDNA multiplied and increased during embryonic development - a phenomenon known as “reversion”.
The panel concluded that reversion did not pose a serious risk and pointed out that pre-natal screening techniques would be able to pick it up before a woman gave birth.
Professor Doug Turnbull, from the University of Newcastle, said: “This is obviously great news with the report conclusions. This gives women who have mitochondrial DNA mutations reproductive choice and I am delighted for them.”
Robert Meadowcroft, chief executive of Muscular Dystrophy UK, which supports families affected by mitochondrial diseases, said: “We wholeheartedly support the positive recommendations for mitochondrial donation IVF to be cautiously implemented in clinical practice, for carefully selected patients.
“This pioneering technique could give women with mitochondrial disease the chance to have a healthy child, without the fear of passing on this condition which can lead to ... multiple disabilities and indeed life-limiting impairments.
“We are thrilled to see how the procedure has advanced and look forward to the possibility that it may shortly be available to eligible women at specialist clinics.”
However not everyone is in favour of women receiving the treatments.
Dr David Clancy, from the faculty of health and medicine at the University of Lancaster, said the technique was “currently imperfect”.
He maintained that the risk of carry-over and reversion could lead to as many as one in 30 women receiving mitochondrial replacement therapy giving birth to a child with an inherited disease.
Dr Clancy added: “By the intervention that is MRT (mitochondrial replacement therapy), the evidence now suggests that, at some point, producing a child who will suffer from mitochondrial disease is a certainty. Are we, as a society, okay with that?”
Mary Herbert, Professor of Reproductive Biology at the Wellcome Trust Centre for Mitochondrial Research at the University of Newcastle, said her team was “ready” to submit an application to offer women mitochondrial replacement therapy once the go-ahead was given by the HFEA.
The treatments at the Newcastle Fertility Centre would mark the start of a “comprehensive” NHS-funded programme.
Prof Herbert said: “We have seen a number of women with mitochondrial DNA mutations for whom the treatment would be appropriate. We’re hoping to treat up to 25 a year.
“The start date will depend on how long it takes to process the licence applications and to finalise NHS funding.”
She added: “It is really gratifying for us to be able to extend the scope of reproductive technologies to help families affected by these dreadful diseases and it will be a great privilege to see our work over the past decade finally come to fruition.
“Our research efforts over the next five years will focus on refining the techniques to further reduce the risk of disease transmission.”