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Medical research: Evaluating mitochondrial replacement in families with mitochondrial diseaseAdd to my bookmarks


December 1, 2016

Mitochondria carrying disease-causing mutations have, in human eggs, been replaced with healthy donor mitochondria in a small proof-of-principle study published online in Nature this week. The work outlines key requirements for conducting clinical trials to assess the potential of mitochondrial replacement therapy (MRT) for preventing the transmission of mitochondrial disease from mother to child.

Mutations in mitochondrial DNA (mtDNA), which are inherited from the mother, are associated with various severe or fatal syndromes. In egg cells, replacing mitochondria carrying mutated mtDNA with healthy mitochondria from a donor egg could potentially be used to prevent the transmission of harmful mtDNA mutations from mother to child. Yet, although proof-of-principle studies of MRT have been conducted using carrier eggs with normal mtDNA, MRT has not been evaluated using eggs from women with mtDNA-associated syndromes.

Shoukhrat Mitalipov and colleagues report the outcomes of MRT in three families with a neurological disorder known as Leigh syndrome and one family with a neurodegenerative syndrome called MELAS. They used a technique known as maternal spindle transfer in which the maternal DNA and spindle from the egg of a carrier mother is transferred to a donor egg (whose nuclear DNA has been removed) that carries only healthy mtDNA, which is then fertilized and cultured up to the blastocyst, or implantation, stage.

The resulting embryos contained more than 99% donor mtDNA, and donor mtDNA remained stable in embryonic stem cells derived from most embryos, although some embryonic stem cell lines showed signs of reverting to the maternal mitochondrial genetic profile (haplotype). The reasons for this drift remain uncertain, although the authors suggest that certain genetic variations (polymorphisms) in mtDNA might contribute to the maternal haplotype being amplified. They propose a matching paradigm that could help to select compatible donor mtDNA for MRT, although additional studies are needed to evaluate this.

DOI:10.1038/nature20592 | Original article

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