Is it Possible to Have Three Genetic Parents?

Written by on February 27, 2015 in Research & Technology - No comments

The British House of Commons recently voted to allow a new fertility treatment called mitochondrial DNA replacement therapy. While this won’t become a law until it is also approved by the House of Lords, they are the first country in the world that may soon offer an IVF technique that creates a baby with genetic material from three different individuals. The US FDA has begun hearings to consider granting approval for this technique as well, but has not yet reached a decision.

PregnancyWEBThe technique to modify maternal mitochondrial DNA (mtDNA) has been developed to help women with mutations in their mitochondrial DNA give birth to offspring who are free of mitochondrial disease. The disease is passed on to offspring either through mutations in the maternal mtDNA or in mutations of nuclear DNA that alter mitochondrial function. Currently, there is no curative treatment for patients affected by mitochondrial disease, so the focus has been on preventing the inheritance of the condition.

Mitochondrial disease is relatively rare, affecting an estimated 11.5 per 100,000 people3. Mutations in mitochondrial function do not lead to the development of one specific disease, rather they create a group of clinically heterogeneous diseases. Since mitochondria are responsible for supplying cellular energy via ATP production, mitochondrial disease tends to affect high energy requiring tissues like the brain, muscle, liver, heart, kidney, and CNS2. Symptoms associated with the disease include blindness, muscle wasting, deafness, diabetes, seizures, neuropathy, and organ failure3.

Prenatal testing and interpretation for mitochondrial disease is difficult because each individual cell can contain a mixture of both normal and abnormal mtDNA, referred to as heteroplasmy. The percentage of abnormal mtDNA that is seen in a chorionic villus sample may not adequately reflect the percentage of abnormal mtDNA that is present in the rest of the fetal tissue. Additionally, the percentage level may change as the fetus continuous to develop and can continue to change throughout the person’s entire lifetime3. These same limitations for prenatal testing exist for preimplantation genetics as well.

A woman who is at high risk for having offspring affected by mitochondrial disease can use donor oocytes to insure against having an affected child. However, this option does not allow for her to have a genetic link to her children, which isn’t always an optimal choice. By using only the mitochondrial DNA from a donor, a woman can insure that she has an unaffected child while still maintaining a genetic link to that child.

Several techniques have been developed that would make it possible to use a donor’s mitochondrial DNA. While using different methods, all techniques involve injecting the cellular material from a healthy donor egg into an unfertilized egg from a women with mitochondrial disease before undergoing in vitro fertilization.  The transferred ooplasm would thus contain the genetic material from three different individuals.

Concerns about this technique among scientists are that potential mismatches between the donor and the host could cause unanticipated problems. Many argue that not enough is known about the long term consequences of this technique to pursue its use in human patients1. Since this technique permanently alters the genetics of the future child, any problems could be passed on to future generations.

It is estimated that approximately 150 women per year could benefit from this new technique in the UK4. So while its use would not be broad, it would offer a new opportunity for reproduction to a group of women who previously had few options.

References:

1. Vogel g, Stokstad E. U.K. Parliament approves controversial three-parent mitochondrial gene therapy. Science Magazine. http://news.sciencemag.org/biology/2015/02/u-k-parliament-approves-controversial-three-parent-mitochondrial-gene-therapy. Feb. 3, 2015. Accessed Feb. 13, 2015

2. Amato P, Tachibana M, Sparman M, Mitalipov S. Three-Parent IVF: Gene replacement for the prevention of inherited mitochondrial diseases. Fertil Steril. 2014 Jan;101(1):31-35.

3. Chinnery P. Mitochondrial disorders overview. In: Pagon RA, et al. GeneReviews. Seattle, WA: University of Washington, Seattle;1993-2015.

4. Gorman G, et al. Mitochondrial donation- How many women could benefit? NEJM. 2015 Jan DOI: 10.1056/NEJMc1500960.

By Carrie A Noriega, MD

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