Mitochondrial Replacement Techniques Are ‘Ethically Permissible’ and Worthy of Clinical Study, US Panel Advises

Three researchers were brought together by the Institute of Medicine (IOM) to consider the ethics, guidelines, and potential risks of mitochondrial replacement techniques (MRTs) aiming to prevent mother-to-child transmission of mitochondrial diseases. Their article, “Mitochondrial Replacement Techniques — Implications for the Clinical Community,” was published in The New England Journal of Medicine.

Mitochondrial DNA (mtDNA) diseases are a group of very heterogeneous disorders transmitted from mother to child, due to defective DNA present on mitochondria, the energy-producing organelles of cells. There are more than 400 known pathogenic mutations in the mitochondrial genome, which contains only 37 genes. These diseases, which can vary greatly in severity and age onset, can affect different organs and systems. Symptom management is the approach often employed by doctors, as there currently are no cures or Food and Drug Administration (FDA)-approved therapies for any mtDNA disease.

Reproductive scientists have focused their efforts on preventing transmission of mitochondrial diseases by MRTs, in which the mitochondria harboring disease-causing mutations are replaced in the mother’s oocytes or zygotes with mitochondria containing healthy mtDNA genomes. In fact, as the authors wrote in the article’s opening sentence,  “Mitochondrial DNA (mtDNA) disease may be the poster child for highly targeted, ‘personalized’ medicine.”

The IOM Committee on the Ethical and Social Policy Considerations of Novel Techniques for Prevention of Maternal Transmission of Mitochondrial DNA Diseases, done at the request of the U.S. Food and Drug Administration (FDA), considered the ethics and risks of clinical investigations of MRTs in humans. According to the article, written by Marni J. Falk, MD, director of the Mitochondrial-Genetics Clinic at The Children’s Hospital of Philadelphia, and co-authored by Jeffrey Kahn, PhD, MPH, of the Johns Hopkins Berman Institute of Bioethics, and Alan Decherney, MD, an obstetrician-gynecologist and reproductive endocrinologist at the National Institute of Child Health and Human Development, the panel concluded that “it is ethically permissible to conduct clinical investigations of MRT[s], subject to certain conditions and principles.”

Such guidelines include predominant focus on the child’s safety and, therefore, recommend that MRTs be initially conducted in male embryos, since only women can transmit mtDNA diseases to a child. The panel also recommended that, with the goal of further limiting the use of these techniques to appropriate patients, the FDA should formulate and implement clear policies, and professional societies should issue clear practice recommendations. Moreover, the extended monitoring — “probably well into adulthood” — of children conceived after MRT is highly recommended.

Finally, the panel also recommended that researchers investigate possible health problems before regulatory approval or clinical use of the techniques, as these procedures involve mixing mitochondrial DNA from a female donor with DNA from the nucleus of the mother and father.