October 16, 2014

expert reaction to latest expert review on the science of preventing mitochondrial disease

The Human Fertilisation and Embryology Authority (HFEA) has issued an addendum to their report on mitochondrial donation techniques, reviewing polar body transfer (PBT).

Prof Justin St. John, Centre for Genetic Diseases, MIMR-PHI Institute of Medical Research, Monash University, said:

I agree that PBT is still in its infancy and that a number of studies should be conducted to determine whether the technique is safe and appropriate to use to treat women who are carriers of mitochondrial disease. However, PBT is one of three proposed techniques and each requires further validation, as proposed in the report. My concern is that each technique is different and may give rise to different patterns of mitochondrial DNA transmission and selection of any accompanying defective mitochondrial DNA. Therefore, each technique should be fully validated in this respect. As well as analysing fetal development in a non-human primate model, it is essential to analyse offspring to determine that no abnormalities appear at least during early life.

Prof Frances Flinter, Consultant in Clinical Genetics and Caldicott Guardian, Guy’s & St Thomas’ NHS Foundation Trust, said:

“Patients affected by serious mitochondrial disorders will be encouraged to hear about the possibility of a third option that may help them have a healthy baby, even if, at this stage, less is known about polar body transfer. However, until Parliament changes the regulations that currently mean all of these potential therapies are illegal, no-one can be offered therapy as part of a carefully controlled clinical trial.”

Alastair Kent OBE, Director, Genetic Alliance UK, said

“This is a third credible approach to avoiding mitochondrial DNA conditions. While continuing to explore all promising avenues that may help at risk families, we should remember that we are further along the road with two other techniques (pronuclear transfer and metaphase II spindle transfer), and press on with implementing regulations that will allow affected families to benefit as soon as the science is ready.”

Dr Frances Rawle, Head of Policy at the Medical Research Council, said:

“The MRC welcomes the HFEA scientific report on polar body transfer to treat the serious diseases resulting from abnormal mitochondrial function.  This new approach demonstrates the continuing rapid progress towards potential therapies in this field and the report equally demonstrates the careful expert scrutiny being applied to guide a decision on when such techniques could be tried in humans.

“Once the scientific evidence is judged by the HFEA to be sufficient, it’s important that the appropriate regulations are put in place to allow the techniques to be tried in patients without unnecessary delay.”

Prof Doug Turnbull, Professor of Neurology, Newcastle University, said:

“The most recent HFEA scientific report describes how a new technique – polar body transfer – has promise to prevent the transmission of mitochondrial DNA disease. This is good news and it is important that a number of options are available; but it is to be stressed that the technique is at an early stage, whereas the pronuclear transfer and metaphase II spindle transfer have been established in human eggs and embryos. This report should add to the urgency of debating the passing of regulations in Parliament.  The regulations are about the principle of preventing these diseases from being transmitted and as more countries become involved in the science the importance of making this a possibility for patients in the UK is even more important.”

Dr Dusko Ilic, Senior Lecturer in Stem Cell Science, King’s College London, said:

“Mitochondrial diseases are absolutely devastating to individuals and families, and as a society we have a moral obligation to help those affected wherever possible. Here we have an opportunity to help, but we are endlessly debating about passing regulations in Parliament because of unjustified safety concerns.

“Worries that the mitochondrial genome will somehow affect the phenotype of the baby are baseless. Mitochondrial DNA encodes only 37 genes, whereas the nuclear genome codes for 20,000-30,000 genes. All mitochondrial genes code for proteins which play a role in metabolism, and speculations about other roles of mitochondrial genes such as their influence on the nuclear genome are only speculations and nothing else. The phenotype of a child is likely to be affected more by the maternal metabolic environment of a surrogate mother than by a new set of mitochondria, and we have now completely accepted surrogacy.

“The recently described technique of polar body transfer seems to be to some extent better, simpler and safer, than metaphase II spindle transfer. However the technique is relatively new, demonstrated only in mice, and it will take years of scrutinizing further experiments in addition to studies in primates to be sure that it will work in humans too. I do not see the need in waiting for this further validation to happen before licensing, when we already have something which we know can work and is not unsafe. We should not delay a decision on approval until this new method is at a further stage of development several years down the road, nor should we do this for future potential techniques.

“Biotechnology is a dynamic science. New, better, and more efficient techniques are under development all the time. We should push ahead with further validation of techniques which we know to work in other organisms and which we know are not unsafe, so that their potential for use in humans can be translated to beneficial therapy.”

Dr Jeremy Farrar, Director of the Wellcome Trust, said:

“The independent scientific panel report considers an alternative technique to those currently being proposed for mitochondrial donation. The polar body transfer technique looks very promising for patients with mitochondrial disease, but will require further research before being able to be considered for use in patients. There are already other techniques for avoiding mitochondrial disease which are ready to be used in patients, access to which is awaiting regulations. The same scientific panel has found no safety reasons not to proceed with these techniques, which also have broad public and ethical support. Therefore we urge the government to introduce regulations now to avoid further delay and give families affected by mitochondrial disease the reproductive choice to have a healthy child.”

Sarah Norcross, Director of the Progress Educational Trust, said:

“It is no surprise that scientists in various countries are at different stages in researching different techniques to overcome these debilitating mitochondrial diseases. The UK Government should not delay in passing regulations while researchers in other countries catch up, but instead should move forward, so that patients here can benefit from the techniques that are close to being ready for use in clinical studies.”

‘A lay summary and “polar body transfer” addendum to third report on safety and efficacy of mitochondrial donation techniques’ published by the Human Fertilisation and Embryology Authority (HFEA) Thursday 16 October 2014.

Declared interests

None declared