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

The study in NEJM is very important and represents a breakthrough in mitochondrial medicine. It should be remembered mitochondrial diseases can be devastating and cause substantial suffering in affected children, sometimes leading to an early death. Families are profoundly affected and the paper in NEJM describe how birth of affected children can be prevented by mitochondrial donation. This advanced procedure is not a disease-treatment but rather an intervention that minimizes the transmission of mutated mtDNA from mother to child. For affected families this is a very important reproductive option. The paper describes a relatively small series of 8 babies born after mitochondrial donation by pronuclear transfer. The paper is carefully done and of very high quality but as always in science the results need to be confirmed by independent studies. Also, long-term clinical follow-up studies of born babies will give additional information about the safety and efficacy of mitochondrial donation.

Before this procedure was applied to human reproduction there was a very long development and evaluation process. There has been a lot of constructive discussion in the scientific community, and the UK Parliament approved legislation allowing mitochondrial donation in 2015.

Mitochondrial donation by the pronuclear transfer procedure always leads to carry-over of some mitochondria from the mother and mutant mtDNA can be transferred. The data presented in the NEJM paper shows that mutant mtDNA was not detected in blood of 5 of the born children. However, in three children, low levels of mutant mtDNA were detected in blood. These low levels of mutant mtDNA are unlikely to cause mitochondrial disease but additional follow-up studies are needed. As pointed out by the authors, the mitochondrial donation by pronuclear transfer should be regarded as a risk-reduction strategy. As always, when it comes to new medical procedures there is a need for validation by independent studies. Also, additional long-term follow-up studies of children born after mitochondrial donation will be needed.

The authors report that the transferred mtDNA has no mutations and the donor mtDNA is therefore unlikely to cause disease or impact ageing. During normal ageing, mtDNA acquires mutations (somatic mutations), e.g., during the massive cell division when the embryo is formed and develops. These mutations are typically present at low levels but accumulate to high levels in a subset of cells in many different ageing tissues. The mitochondrial donation involves transfer of mtDNA without mutations and there is no reason to believe that the donor mtDNA will additionally impact the ageing process.

When it comes disease-causing mtDNA mutations that are present in all copies (i.e., homoplasmic mtDNA mutations) there is currently no alternative to mitochondrial donation to prevent transmission of mutated mtDNA from mother to child. It is possible that alternate methods will be available in the future, e.g., correction of mutant mtDNA by gene editing techniques. There are currently a few promising pharmacological therapies for mitochondrial disease, e.g., nucleoside therapy for mtDNA depletion disorders. It is likely that more treatments will be available in the near future because this field is rapidly developing