Research press release



Medical research: Evaluating mitochondrial replacement in families with mitochondrial disease



今回、Shoukhrat Mitalipovの研究グループは、神経疾患の一種であるリー脳症の3家系と神経変性症候群の一種であるMELASの1家系にMRTを実施した結果について報告している。Mitalipovたちは、母体紡錘体移植という技術を用い、病原性mtDNA変異を持つ母親の卵母細胞に由来する母親のDNAと紡錘体を健康なmtDNAだけを持つドナーの卵母細胞(核DNAを除去した状態)に移植し、受精させ、胚盤胞期または着床期まで培養した。


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

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