Is a therapy designed to treat mitochondrial disease setting its sights on age?

Decoy

It was supposed to prevent the passing on of debilitating and deadly diseases. But much of the recent buzz around mitochondrial replacement is about treating unexplained or age-related infertility.

Mitochondria provide the power for our cells, and when they malfunction, it can be serious. So scientists have developed experimental treatments that use healthy mitochondria from donor eggs. 

In one variation, the nuclear DNA is removed from a donor egg and replaced with the nuclear DNA from an intended mother's egg; the donor egg's mitochondria, left behind in the cytoplasm, provide the power pack. The egg is then fertilized. In another variation, both an egg from a donor and an egg from the mother are fertilized before that swap takes place. Almost all of a person's DNA is in the nucleus, and almost all traits are determined by this nuclear DNA, but mitochondria also contain a small amount of DNA. This means that any child born from such a therapy will inherit DNA from three people — the mother, the father and the donor — which has given rise to terms like 'three-person IVF' and 'three-parent baby.'

The treatments have been controversial since the outset, because it's not yet known whether there will be unintended side effects. It's not easy to leave behind all the faulty mitochondria, for instance, and no one knows whether problems will arise if mitochondria from two different people end up together in a cell. Questions like these are important because any changes to the pool of mitochondria can be passed down to subsequent generations.

Nonetheless, some people argue that the risk is acceptable if the result is prevention of serious disease. In 2015, the UK became the first country to allow mitochondrial replacement therapy, albeit only under strict conditions and with a license. (No such babies have been born there so far.) In 2016, mitochondrial replacement was used to bring a boy into the world for a couple who had already lost two previous children to a mitochondrial disease. (The scientist was American, the couple was Jordanian and the treatment took place in Mexico.) Neither Canada nor the US currently permit it.

Then in 2017, something new happened: mitochondrial replacement therapy was used not in an effort to avoid mitochondrial disease but rather to treat infertility. A child was born to a woman who'd reportedly suffered infertility for 15 years. The treatment was in Ukraine. (That clinic claims to have other pregnancies in progress, and is actively researching a new mitochondrial replacement technique specifically to treat infertility in women over age 42.) Last month, news broke of a baby born to another infertile woman following mitochondrial replacement, this time in Greece. She was 32 years old and had suffered four failed IVFs. She is one of 25 women being recruited for a clinical trial to study the technique to treat infertility.

"It's really troubling," says Marcy Darnovsky, executive director of the Center for Genetics and Society (CGS), based in Berkeley. Darnovsky points out that just two failed IVF cycles qualify a woman to participate in the Greek clinical trial — despite the fact that the link between mitochondrial quality and infertility is little more than "a hunch."

Despite the lack of firm evidence, there have long been suspicions about a connection. More than two decades ago, 17 babies were born in the US after fluid containing healthy mitochondria from donors was injected into their mothers' eggs. (The technique was forbidden after genetic anomalies were found in some fetuses.) More recently, the treatment Augment was also premised on the idea that poor-quality mitochondria were getting in the way of pregnancy. (With Augment, a mother's own mitochondria were used.) "It's a lucrative market," says Darnovsky.

According to a recent post in Biopolitical Times, a CGS publication, all reported births from the therapy after the first one in 2016 have been the result of treatment for infertility, not disease. The author characterizes this as "a nimble fertility industry tapping bigger markets in what could be described... as an off-label use." Meanwhile, earlier this month, interested parties gathered at Harvard Law School to discuss the US situation. Many argued for legalization of mitochondrial therapy — to treat disease, of course. 

Related links:

"Everything you wanted to know about '3-parent' babies" New Scientist, 28 Sep 2016

"First baby born using 3-parent technique to treat infertility" New Scientist, 18 Jan 2017

"First 3-parent baby born in clinical trial to treat infertility" New Scientist, 11 Apr 2019

"Three-person IVF: From genetic disease to genetic design?" Biopolitical Times, 26 Mar 2019

"U.S. researcher says he's ready to start four pregnancies with 'three-parent' embryos' STAT News, 18 Apr 2019

"US scientists push for mitochondrial donation legalisation" BioNews, 29 April 2019

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A shout-out to Eva Voinigescu, a colleague who met with me to discuss HeyReprotech one year ago this week, and whose moral and technical support helped me launch this newsletter.

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Email me at alison.motluk@gmail.com. 

Follow @HeyReprotech on Twitter.