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MITOCHONDRIAL REPLACEMENT THERAPY’S BENEFITS AND OBSTACLES

   Cedric Dent 기자   2018-04-11 14:11
Photo By Aldona Griskeviciene via Shutterstock

 

There are all sorts of diseases with which children are born solely because their mothers transmit said diseases to them. These are referred to as mitochondrial DNA diseases. Many such diseases, at present, can only be treated, not cured, and they’re the result of mitochondrial DNA mutations — genetic defects that get called birth defects when those children are born with them. Treatment only really addresses the symptoms of these diseases because there’s just no known way to change how gene mutations express themselves. Researchers are now calling for the US government to lift the mitochondrial replacement therapy moratorium, however — a controversial ban on a preemptive alternative.

Medical science researchers and experts on medical tort law are now advocating the US federal government make mitochondrial replacement therapy permissible to preempt fatal illnesses altogether. Mothers who bear mtDNA mutations can easily and frequently do transmit them to their children, and those mutations are expressed as fatal and incurable illnesses. Despite this, there is a form of mitochondrial DNA that has been researched very extensively and has been found capable of preventing that transmission to offspring. This is why two researchers are now contending that the ban on mitochondrial replacement be lifted.

At the very least, these researchers are saying that there needs to be reconsideration for a public process that engages media, medical professionals, Congress and the US Food and Drug Administration. These researchers are Brown University medical science professor Eli Adashi of the Warren Alpert Medical School and Harvard Law professor I. Glenn Cohen. They published their argument in the form of a study in Obstetrics & Gynecology. The process they’re advocating is one intended to elucidate advantages of mitochondrial replacement, chiefly referring to children being born healthily. This process is also intended to divorce it from the controversial embryonic gene editing issue, according to Adashi and Cohen.

 

 

As a therapy, mitochondrial replacement just supplants mutation-bearing mitochondria in unfertilized eggs with mutation-free mitochondria donated like blood or plasma. “A thousand children are born every year in the U.S. with serious, life-threatening issues that in a better world could be prevented by mitochondrial replacement,” according to Adashi. “While I have every respect for the sanctity of life, this issue is not about the sanctity of life. There is an inherent hypocrisy in holding this procedure hostage at the expense of 1,000 children each year who are doomed to die a painful death. There is nothing anti-life about the procedure, because no embryo is destroyed, and the life of the baby is saved.”

This all has to do with legislation passed back in 2016 wherein American research was prohibited from pursuing any procedure in which human embryos were modified or created. Adashi notes that it’s very much a fact that mitochondrial replacement doesn’t modify the nuclear genome; nevertheless, the process of supplanting mutated mitochondria with mutation-free mitochondria is a process currently categorized as embryonic modification and, thus, is prohibited by that 2016 law. Adashi and Cohen also go further to highlight the fact that the authors of that 2016 law are actually anonymous and that the law was passed without any floor discussion, congressional hearing or public engagement, which they use as a reason to suggest that all three of those things should be done before this issue is dismissed again.

Adashi and Cohen also remind readers that the whole point of the law was to prevent embryo loss, which is a purpose that has nothing to do with mitochondrial replacement. That’s why they want a public process to review just mitochondrial replacement by itself to determine what they feel is obvious, which is that it shouldn’t be banned when it can only save lives and can, in no known way, endanger them. “Mitochondrial replacement is best viewed as life-enhancing in its outlook by dint of its capacity to alleviate human suffering in a context where no other option exists,” they write.

 

Photo By Naeblys via Shutterstock

 

Back in January, a column was published in Nature Reviews Molecular Cell Biology entitled, “Progress in mitochondrial replacement therapies.” In it, the authors explained the challenges that new technology for preventing mtDNA from transmitting its mutations from mother to child is facing. They also allude to numerous proof-of-concept studies for metaphase II and pronuclear spindle transfers both being found to be feasible means of developing mutation-free, maternal DNA in early-stage human embryos.

There’s a preponderance of evidence to suggest that mtDNA replacement therapy is now fit for clinical evaluation according to that study, which predates Adashi’s and Cohen’s publication. The study does concede, however, that there are minimal risks. The most significant risk discussed is the possibility that nuclear and mtDNA might end up being a haplogroup mismatch, which is the mtDNA replacement therapy equivalent of organ rejection in the event of a person receiving an organ from someone else. In other words, it’s a rare but possible occurrence.

An additional challenge to take into consideration, though, is that there aren’t really that many human eggs available for research on a normal basis, yet the far bigger obstacle in that regard is that it won’t matter so long as legislation in the US bulwarks progress. In the same year that the U.S. was essentially outlawing mitochondrial replacement therapy (not directly but inadvertently by outlawing a broad category of concerns), the UK was actually giving the therapy itself the go-ahead. This came after prolonged ethical reviews; four distinct, independent scientific reviews; public consultations; and debates in both houses of Parliament. The first British license for a medical center to administer this therapy was approved just last year in fact.

[researchpaper 리서치페이퍼=Cedric Dent 기자]

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