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Mix and Match: Babies with DNA from More Than Two Parents Is a Thing

mitochondrial replacement therapy in action

Reproductive science has achieved some pretty incredible feats over the last few decades. Various techniques to treat infertility including in vitro fertilization has allowed thousands of couples have children. Likewise, implantation techniques have similarly improved as has accessibility to care. It should therefore be of little surprise that advances in the field continue and involve highly complex procedures. The latest of these is termed mitochondrial replacement therapy, which attempts to prevent severe genetic diseases from occurring. This technique, though infrequently performed, replaces mitochondrial DNA to protect a fetus from specific illnesses. And it’s worth noting this DNA doesn’t come from either parent but instead from a donor.

mitochondrial replacement therapy under a microscope
Want some extra DNA for your fetus? Mitochondrial replacement therapy has got you covered.

Understanding this, one can see that the fertilized embryo contains DNA from three different sources. In addition to sperm DNA and nuclear DNA from the mother, a donor’s mitochondrial DNA is also included. Because some severe inherited diseases arise from defective mitochondrial DNA, mitochondrial replacement therapy reduces this risk. This is especially true for mothers who have a family history of such disorders. But at the same time, the procedure is associated with some unknown and some ethical concerns. These concerns as well as the cost of the procedure is why adoption has been slow. Regardless, it shows once again just how advanced genetic therapies have become as well as their incredible potential.

(Genetic diseases are being fought with precision medicine–read more on this innovation in this Bold story.)

“All applications for [mitochondrial replacement therapy] are assessed on an individual basis against the tests set out in the law and only after independent advice from experts.” – Peter Thompson, CEO of the Human Fertilization and Embryology Authority (HFEA), UK.

The History of Mitochondrial Replacement Therapy

For most of us, the notion of mitochondrial replacement therapy is new. But for researchers in the field, the concept dates back to the late 1990s. It was then that scientists began to consider replacing mitochondrial DNA as a means to prevent horrific genetic diseases. Animal studies then began in the early 2000s on mice and non-human primates. These showed highly favorable results, and as such, led to some countries approving the procedure. The United Kingdom was first to do so in 2015, and they currently have the most cases. Other countries also now include the U.S., Greece and Ukraine. All of these countries have notable criteria that must be met in order for its use to be considered.

In terms of actually performing mitochondrial replacement therapy on human subjects, Mexico was actually the first to achieve this. They announced a successful first case in 2016. Ukraine then reported the second case of replacing mitochondrial DNA with a donor in 2017. Greece then did so in 2019. However, recent reports out of the U.K. indicate some programs are expanding at a faster pace. The University of Newcastle along with the Newcastle Fertility Center has now performed 32 of these procedures. To date, less than five babies have been born after receiving mitochondrial replacement therapy. Thus, it seems these techniques may become more common in the near future in some countries.

some parents constructing a superhero
Adding more DNA to a fetus is a great first step in making a superhero… right?

The Process of Replacing Mitochondrial DNA

In order to appreciate the advances in DNA therapies, it’s important to have some concept of how mitochondrial DNA replacement occurs. The process itself first involves collected eggs from the mother and then removing the nucleus from the eggs. The nucleus contains DNA from the mother, and this is transferred to a donor egg replacing its nucleus. However, the donor egg also has DNA in its mitochondria, which remains. Once this is completed, the donor egg is fertilized with a single sperm before being implanted into the mother’s womb. This is how mitochondrial replacement therapy has three sources of DNA content.

The end result of this process is eliminating maternal mitochondrial DNA and replacing it with donor mitochondrial DNA. In normal fertilization, nearly all the DNA in the mitochondria come from the mother. Mitochondria exist within each cell and are responsible for generating cellular energy among other things. But the DNA within these organelles have been linked to several genetic diseases. These includes conditions such as Leigh’s Syndrome, MELAS Syndrome, and MERRF Syndrome. For mothers with a strong family history of such conditions, mitochondrial replacement therapy could be protective. In fact, it might even protect subsequent generations.

“It will be interesting to know how well the MRT technique worked at a practical level, whether the babies are free of mitochondrial disease, and whether there is any risk of them developing problems later in life or, if female, if their offspring are at risk of having the disease.” – Robin Lovell-Badge, Stem Cell Biologist and Developmental Geneticist, Francis Crick Institute

Moving Forward with Caution

mitochondrial DNA in a bunch of test tubes
Tweaking mitochondrial DNA means you and your spouse can add some extra traits to your future kids.

As with any new medical techniques, some unknowns and risks do exist with mitochondrial replacement therapy. For example, while studies demonstrate positive outcomes and safety results, long-term effects on health and development have yet to be proven. Because the degree to which mitochondrial DNA and DNA in a cell nucleus is not fully known, this too poses risks. As a result, there could be some alterations affecting metabolism and cell function that has yet to be appreciated. And any time a DNA germline is changed, there exist some ethical concerns about how it might be used. The hope, of course, is that this technique will only enhance health by reducing diseases rather than triggering new problems.

Because of these risks, most countries that have approved mitochondrial replacement therapy are proceeding slowly. This is even true in the UK where the procedure has been utilized more often. Only certain mothers at risk for passing along mitochondrial DNA disorders quality for consideration. Because these diseases are potentially so severe, the risks of mitochondrial replacement are believed to be justified. If this proves to be effective over time, there is also the potential the procedure might be refined to prevent other genetic disorders. Given this, it’s clear that we are entering into an era of genetic therapies that’s facilitating personalized medicine. Mitochondrial replacement therapy is a bold step in this direction.

 

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