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

Mitochondrial diseases are a group of chronic metabolic disorders that can be fatal. These diseases are caused by mutations in the human genome, which consists of nuclear DNA and mitochondrial DNA. In particular, metabolic disorders caused by mutations in mitochondrial DNA, which affect one in five thousand people, are maternally inherited and currently incurable. In recent years, there have been major advancements in the development of strategies for the treatment or prevention of genetic disorders caused by mutations in nuclear DNA. In contrast, similar strategies for diseases caused by alterations in mitochondrial DNA have remained largely understudied.

Aiming to establish a preventive strategy for metabolic diseases caused by mitochondrial DNA mutations, the authors of this pair of studies published in the New England Journal of Medicine developed an integrated program of preimplantation genetic testing and pronuclear transfer (PGT and PNT, respectively). In this program, female patients carrying mitochondrial mutations underwent PGT to identify embryos with low levels of mitochondrial DNA mutations. In cases where an embryo with these characteristics was identified, the embryo was implanted in the patient and the course of the pregnancy was monitored. In addition, in cases where it was not possible to identify embryos with low levels of genetic alterations, the patients underwent PNT, a procedure in which mitochondrial DNA without mutations is obtained from a donor.

Encouragingly, through this integrated PGT and PNT program, at the time of publication, the authors have already demonstrated a significant reduction in the maternal transmission of mitochondrial mutations in eight cases. Furthermore, the children born from these cases have shown normal development.

In conclusion, this study represents a major advancement in the field of medical genetics and genomics. Understanding the current limitations of mitochondrial gene editing, which would allow genetic alterations to be corrected in different contexts, the authors chose to explore a procedure that cuts the problem off at the root by preventing the transmission of the mutated genetic material. Furthermore, this pair of studies demonstrates clinical benefits in children who, without the integrated PGT and PNT program, would likely have been born with debilitating or fatal genetic mutations. It will be exciting to see if the benefits are maintained over time, and it will be critical to further develop this integrated process to increase its success rates.