Mitochondrial Replacement Therapy

slide0073_image006To date, the Food and Drug Administration (FDA) has not approved human clinical trials for an in vitro fertilization technique that uses mitochondrial DNA from a healthy donor to attempt to prevent the transmission of mitochondrial disease from one generation to the next.

This procedure, called Mitochondrial Replacement Therapy, proposes to give women with mitochondrial DNA mutations an excellent chance of having a child that is over 99% genetically matched with her and her partner, and most importantly, is likely to be free of the mitochondrial disease.

Along with the North American Mitochondrial Disease Consortium (NAMDC), the UMDF presented a webinar to explain Mitochondrial Replacement Therapy and its implications.  The webinar was moderated by UMDF Science and Alliance Officer Philip Yeske, Ph.D.

Joining the webinar from NAMDC was Michio Hirano, M.D., Chief of Neuromuscular Division at Columbia University Medical Center and Co-Director of NAMDC; Dieter Egli, Ph.D., Assistant Professor of Developmental Cell Biology (in Pediatrics), Columbia University Medical Center and Senior Research Fellow, New York Stem Cell Foundation; and Mark Sauer M.D., Vice Chairman and Chief of the Division of Reproductive Endocrinology and Infertility, Columbia University Medical Center and Director Center for Women’s Reproductive Care.

UMDF’s Position


November 2017

The United Mitochondrial Disease Foundation (UMDF) maintains that every individual has the right to safe and effective health care as well as access to all current therapeutic innovations for the alleviation and prevention of mitochondrial diseases.

Mitochondria are cellular components that contain their own DNA (mtDNA) and are responsible for generating more than 90% of the body’s energy. About one in 200 people is born with a pathogenic mtDNA mutation and one in 5,000-10,000 people develop a symptomatic mitochondrial disease. However, the incidence rates may be higher considering the difficulty of accurate diagnosis and the diversity of clinical presentations.

Most pathogenic mtDNA mutations affect children, who frequently suffer catastrophic organ failure. In adults, the symptoms worsen with age and often become debilitating. Mitochondrial dysfunction typically damages cells of the brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems. Currently, treatment is limited to symptomatic management using vitamins and supplements.

There is an important unmet clinical need to reduce the risk of transmitting mtDNA diseases to offspring. The mtDNA makes up only 0.1% of the entire human DNA and contains 37 genes, distinct from the nuclear DNA, which accounts for 99.9% of a person’s genetic makeup and determine one’s physical appearance and personality. As mitochondria are transmitted exclusively through mothers, a woman with defective mtDNA could potentially use her and her partner’s own nuclear DNA in combination with the healthy mitochondria of a female donor and have a child who is 99.9% genetically identical to her and her partner.

Mitochondrial replacement therapy (MRT) uses healthy mitochondria coming from a donor’s egg whose nucleus has been removed and into which the mother’s nucleus is transferred. In vitro fertilization (either before or after MRT) produces an embryo that contains nuclear DNA from the father and the mother with healthy mtDNA from the donor. This procedure gives women with mtDNA mutations an excellent chance of having their own children, who will be free of the mitochondrial disease.

MRT is NOT genetic manipulation, but rather a technological innovation and an expansion of in vitro fertilization, a clinically-approved technique used for four decades. The latest evidence from leading mitochondrial research institutions in the US and the UK indicate that mitochondrial replacement techniques are safe and effective in primates, although further research will be necessary to fully understand the long-term effects of MRT.

We strongly support further scientific investigation of oocyte MRT as well as constructive debate towards the clinical approval of this therapy in women with mtDNA-related diseases. If demonstrated to be safe and efficacious, this technique should be made available with proper regulatory oversight as an option to families who carry mtDNA point mutations.

Clinical Status

In 2013, the Human Fertilization and Embryology Authority (HFEA) in the UK completed an extensive public consultation on mitochondrial replacement therapy and found widespread support for it. In 2015 the UK Parliament voted to allow mitochondrial donation, and the HFEA is now charged with issuing licenses to practice MRT at UK fertility clinics on a case by case basis. In 2016 the HFEA approved the use of mitochondrial donation in specific cases and in March 2017 the HFEA granted the first clinical mitochondrial donation license to the Newcastle Fertility Centre at the International Centre for Life in Newcastle-upon-Tyne, United Kingdom.

In the US the FDA commissioned the National Academies of Science to convene an esteemed panel of experts to review the scientific, ethical and policy considerations of MRT. In a report issued in February 2016 the committee concluded that it was, on both a scientific and ethical basis, permissible to proceed with clinical testing of MRT with certain limitations. Importantly, the committee emphasized in their final report that concerns about genetic manipulation warrant significant caution and the imposition of restrictions rather than blanket prohibition of MRT to prevent transmission of serious mtDNA disease. Despite this position, the FDA has been prevented from further evaluating clinical applications of MRT by language included in the 2016 congressional spending bill banning the agency from evaluating clinical trials involving genetic modifications that affect the next generation.

In September 2016 it was publically announced that a male child was born earlier in the same year as a result of an MRT technique carried out by a US doctor in a Mexican fertility clinic for the purpose of preventing the transmission of Leigh Syndrome, a form of mitochondrial disease.  Per the announcement at the time, the child is doing well with a very low level of mutant mtDNA. That being said, the editors of the journal that published the findings from Mexico expressed concerns about the approach and treatment process. In August 2017 the FDA posted a letter online informing the clinician who conducted the MRT technique that it is illegal at this time to market the procedure.

Current Trials & Studies


The Columbia Oocyte Mitochondrial Replacement Study (COMRS) is investigating OocyteMitochondrial Replacement(OMR) to prevent transmission of
mitochondrial DNA mutations.  The goal is to investigate the safety and effectiveness of Oocyte Mitochondrial Replacement (OMR) as means to prevent transmission of mtDNA to offspring.  What is involved? Women who carry mtDNA mutations can participate in this study. They will undergo
the egg harvesting stages of In Vitro Fertilization (IVF), a well-established treatment for many forms of infertility. The nuclear genome of an unaffected
donor’s oocyte will be removed. Then the nuclear DNA from the oocyte with a mtDNA mutation will be transferred into the enucleated oocyte of the donor.
This study will result in embryos that are cryopreserved and will not result in pregnancy. Embryo transfer into the uterus (womb) may be part of a future study that will require approval by the Food and Drug Administration (FDA). Click here for details and contact information.

Oregon Health & Science University Center for Embryonic Cell and Gene Therapy

OHSU is currently recruiting donors for an IRB approved project, Mitochondrial gene replacement in human oocytes #6709. OHSU is working on a clinical study to evaluate mitochondrial replacement in oocytes from carriers with mtDNA mutations. They are recruiting young women (21-33) with children who were diagnosed with inherited mtDNA based disease.   For details, call (503) 346-3540.