Reacción a "First results on babies born with pioneering technology that reduces risk of mitochondrial disease"

I am happy to see that the first results from the Newcastle University group are now finally published, after being granted a license by the HFEA in 2017, and that the eight resulting children are in good health. However, while the results show that the technique is feasible and can lead to a substantial reduction of the mutation load in the resulting children, it also shows that we need to tread very carefully.”“In line with previous research by the group of Nuno Costa-Borges, this research confirms the possibility of reversal (meaning that although there is only a small fraction of the intended mother’s mitochondrial DNA (mtDNA) in the embryo, this fraction sometimes increases substantially as the foetus develops), which could still result in mitochondrial diseases in the resulting children. Fortunately, preliminary research does indicate that while the mutation loads appear to increase between the embryonic phase and birth, they appear to remain stable after birth.”“These are very important results as there was a lot of uncertainty over the safety of MRT. Using PGT when possible and reserving MRT for those cases in which PGT cannot offer a solution was a prudent approach given the experimental nature of MRT. It will be interesting to see more data in the future on whether reversal is more frequent in MRT or PGT, so that the safest procedure can be selected.”“Although the heteroplasmy-levels are limited in this study, it does show that reversal is a real danger for the offspring, which can have serious health implications. At least three things follow from this.”“First, people entering into this and future clinical trials will need to be extensively counselled that this is not a risk-elimination treatment, but a risk-reduction treatment.”

“Second, we need more research into the mechanisms that trigger reversal, so that it can be prevented before this technique is implemented in routine care + We need follow-up research in the children born after MRT.”“Third, it is important to keep in mind that by framing this as a risk-reduction strategy, we are ignoring the possibility of conceiving through a traditional egg donation procedure. While genetic parenthood is evidently important to many people, the trade-off that we are making here is that between a genetically related child with a high risk of mitochondrial disease (natural conception), a genetically related child with a reduced risk of mitochondrial disease (PGT or MRT) and a non-genetically related child with the near-absence of a risk of mitochondrial disease (through donor conception). If people who would have chosen for donor conception now opt for MRT, this is actually a risk-increasing technology, rather than a risk-reducing one.”

“This strategy lowers the risk of mitochondrial disorders in the children when the point of comparison is natural reproduction by the parents, but the safest option is still donor conception, which eliminates the risk of passing on the mitochondrial condition, rather than reducing it.”“While the donor plays an essential role in the birth of the child, attributing them a parenthood-status based on a small genetic contribution appears unwarranted. At the same time it would be correct to call them a ‘genetic progenitor’ or ‘genetic contributor’.”“While the group of Nuno Costa-Borges received a lot of backlash for performing their MRT clinical trial in people with repeated IVF failure, rather than people with mitochondrial diseases, we must acknowledge in hindsight that given the phenomenon of reversal, their approach might have been the more prudent one. In their study they observed reversal in one infant going from <1% of maternal mtDNA at the blastocyst stage to 30-60% (depending on the tissue type) at birth. This was fortunately not a problem as the maternal mtDNA was not disease-causing, but a similar level of reversal may have devastating consequences in a clinical trial in women with mitochondrial disorders, such as the one reported on in the NEJM today.”