Scientists warn of potential mitochondrial replacement IVF health risks

A group of scientists has expressed concerns that it may be too soon to bring mitochondrial replacement (MR) techniques, which are still under development, to the clinic. This follows the recent news that the UK Government will support the introduction of mitochondrial replacement therapy, with the relevant legislation due to be debated in Parliament next year (reported in BioNews 711).

In an article published in the journal Science, three biologists argued that while the availability of MR-assisted therapies is an 'exciting prospect', more time is needed to better understand the techniques in animals before moving on to clinical trials. They explain that there are extensive interactions between mitochondrial DNA and nuclear DNA, and that using donor mitochondria may have long-term consequences that are not yet understood.

'We draw attention to theory and experimental findings that appear to have been overlooked in the scientific and public forums of this debate', the authors wrote in the paper. 'Studies on model organisms, ranging from mice to fruit flies, indicate that MR can profoundly change the expression profiles of nuclear genes and affect a range of important traits such as individual development, cognitive behaviour, and key health parameters'.

MR-assisted IVF has successfully given rise to live offspring in macaque monkeys, but these offspring have not yet reached adulthood. The authors suggest further monitoring the health and fertility of these monkeys.

Klaus Reinhardt of the University of Tuebingen, Germany, lead author of the article, said: 'It is not at all our intention to be a roadblock, we think it is fantastic that for women affected there could be a cure. We are sure that the Human Fertilisation and Embryology Authority (HFEA) will decide [whether to allow the therapy] on a case-by-case basis and will have safeguards. But couples that have mild mitochondrial disease might choose to wait two years until the macaques are a bit more mature'.

MR involves taking the nuclear material out of a prospective mother's egg (thereby leaving behind the faulty mitochondria) and placing this nuclear material into a donor egg which has healthy mitochondria. MR could be used to treat mothers at risk of passing on faulty mitochondria to their children, as this can lead to complex and sometimes fatal mitochondrial disease.

The HFEA, which ran a public consultation in 2012 gathering evidence on the techniques and advised the Government on the evidence surrounding mitochondrial replacement therapy, has said that there is at present no reason to believe the techniques are unsafe.

In a statement, the HFEA said: 'The panel of experts convened by the HFEA to examine the safety and efficacy of mitochondria replacement carefully considered the interaction between nuclear and mitochondrial DNA and concluded that the evidence did not show cause for concern'.

Professor Doug Turnbull, from the mitochondrial research group at Newcastle University shares the HFEA's position. 'One of our prime interests is about the safety of these techniques,' he said. 'Mismatch between the mitochondrial and nuclear genome is a potential risk, but I don't think it's personally as big a risk as they're saying'.

David Thornburn, head of mitochondrial research at Murdoch Childrens Research Institute in Melbourne, Australia said in the New Scientist: 'In a black and white, risk-averse, litigation-averse world it's tempting to say let's wait and first do no harm'.

'To me, that ignores the daily lives and desires of these families', he added.