Reproductive Options for Women with Mitochondrial Disease

Abstract

Pathogenic mutations in mitochondrial DNA (mtDNA) are highly prevalent in the population and can result in a range of isolated organ or multisystem disorders affecting children and adults, collectively known as mtDNA disease. The clinical features of these diseases are extremely variable, ranging from no symptoms or very mild symptoms to severely debilitating disease or death in early infancy. The mitochondrial genome is strictly maternally inherited and so a woman with an mtDNA mutation is at significant risk of passing this to her children through the mitochondria present in her oocytes. The risk is very difficult to predict, however, due to a genetic bottleneck that occurs during development of the female germline. This uncertainty, coupled with the lack of an effective treatment, means that women with mtDNA disease have difficult decisions to make about having children. The current reproductive options available to women with an mtDNA mutation will not be suitable for all. To address this problem, we have developed a novel IVF-based technique to prevent transmission of mtDNA disease. The technique, termed mitochondrial replacement, involves transferring the nuclear DNA from the egg of an affected woman to a donated egg from which the nuclear DNA has been removed. The resulting reconstituted egg would enable the woman to have a child that is genetically related to both parents but with a greatly reduced risk of mtDNA disease. Experiments to determine the safety and efficacy of mitochondrial replacement have been performed and are crucial if this technique is to be considered as a clinical treatment to prevent transmission of mtDNA disease. The use of mitochondrial replacement has ethical and legal implications and requires a change in policy. This has been an extensive process and the proposed technique is to be debated in both Houses of Parliament in early 2015.