Mitochondrial DNA (mtDNA) is a molecule in our cells that contains information about how to build important cellular machines that provide us with the energy required for life. Mutations in mtDNA can prevent our cells from producing these machines correctly, causing serious diseases. Mutant mtDNA can be passed from a carrier mother to her children, and as the amount of mutated mtDNA inherited can vary, children's symptoms can be much more severe (often deadly) than those in the mother.
Several therapies exist to prevent or minimise the inheritance of mutant mtDNA from mother to daughter. These range from simply using a donor mother's eggs (in which case the child inherits no genes from the "mother") to amazing new techniques where a mother's nucleus is transferred into a donor's egg cell which has had its nucleus removed (so that the child inherits nuclear DNA from the mother and father, and healthy mtDNA from the donor). The UK is currently debating whether to allow these new therapies: several potential scientific issues have been identified in their application.
As experiments with human embryos are heavily restricted, experiments in animals provide the bulk of our knowledge about how these therapies may work. We have previously written about our research in mice, highlighting a possible issue arising from mtDNA "segregation", where one type of mtDNA (possibly carrying a harmful mutation) may proliferate over another: this phenomenon could, in some circumstances, nullify the beneficial effects of mtDNA therapies. Another possible issue involves the effects of "mismatching" between the mother and father's nuclear DNA and the donor's mtDNA: current experimental evidence is conflicted regarding the strength of this effect. Finally, mismatch between donor mtDNA and any leftover mother mtDNA may also lead to biological complications.
We have recently written a paper explaining and reviewing the current state of knowledge of these effects, summarising the evidence from existing animal experiments. We are positive about implementing these therapies, which have the potential to prevent the inheritance of devastating diseases. However, we note cautions about this implementation, noting that several scientific questions remain debated or unanswered. We particularly highlight that "haplotype matching", a strategy to ensure that donor and mother mtDNA are as similar as possible, will largely remove these concerns. Iain
Several therapies exist to prevent or minimise the inheritance of mutant mtDNA from mother to daughter. These range from simply using a donor mother's eggs (in which case the child inherits no genes from the "mother") to amazing new techniques where a mother's nucleus is transferred into a donor's egg cell which has had its nucleus removed (so that the child inherits nuclear DNA from the mother and father, and healthy mtDNA from the donor). The UK is currently debating whether to allow these new therapies: several potential scientific issues have been identified in their application.
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| If a mother carries an mtDNA mutation, (A) no clinical intervention can lead to her child inheriting that mutation and developing an mtDNA disease. Several "classical" (B-C) and modern (D-E) strategies exist to attempt to prevent the inheritance of mutant mtDNA, which we review (see paper link below) |
As experiments with human embryos are heavily restricted, experiments in animals provide the bulk of our knowledge about how these therapies may work. We have previously written about our research in mice, highlighting a possible issue arising from mtDNA "segregation", where one type of mtDNA (possibly carrying a harmful mutation) may proliferate over another: this phenomenon could, in some circumstances, nullify the beneficial effects of mtDNA therapies. Another possible issue involves the effects of "mismatching" between the mother and father's nuclear DNA and the donor's mtDNA: current experimental evidence is conflicted regarding the strength of this effect. Finally, mismatch between donor mtDNA and any leftover mother mtDNA may also lead to biological complications.
We have recently written a paper explaining and reviewing the current state of knowledge of these effects, summarising the evidence from existing animal experiments. We are positive about implementing these therapies, which have the potential to prevent the inheritance of devastating diseases. However, we note cautions about this implementation, noting that several scientific questions remain debated or unanswered. We particularly highlight that "haplotype matching", a strategy to ensure that donor and mother mtDNA are as similar as possible, will largely remove these concerns. Iain
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