Mitochondrial Replacement Therapy

slide0073_image006The Food and Drug Administration (FDA) is considering the approval of human clinical trials for a pioneering 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

UMDF Position Statement on Mitochondrial Replacement Therapy

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.

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. Currently, an FDA Advisory Committee in the US is deliberating on scientific, technologic and clinical issues on MRT, with an ultimate goal of making this technique available to women carrying deleterious mtDNA mutations to prevent transmission of mtDNA diseases.

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 as an option to families who carry mtDNA point mutations.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 as an option to families who carry mtDNA point mutations).

Current Trials & Studies

North American Mitochondrial Disease Consortium (NAMDC)

NAMDC is conducting a survey for women 18 years or older who carry (or at risk of carrying) a mitochondrial DNA mutation. The survey is designed to assess the interest level in a possible new technique that would reduce, or even eliminate, the transfer of harmful mitochondrial DNA from a carrier mother to her children. 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. Click here for additional details and contact information.