This week, scientists reported that they were able to treat a serious genetic disorder in the womb — in mice. It sounds like science fiction, but this type of treatment may not be far away for humans. What will we need to figure out before we get there?
For the study published in Nature Medicine, scientists studied the neurodegenerative disorder Gaucher syndrome. Gaucher is caused by mutations in the GBA gene and leads to serious joint pain, convulsions, and cognitive impairment. To treat this, the researchers injected the fetus with a virus engineered to carry working (non-mutated) copies of the GBA gene to replace the mutated ones.
It wasn’t a perfect fix. The mice lived for 130 days instead of five days, but they did have some signs of brain inflammation, according to study co-author Simon Waddington.
But while it’s a promising step to treat a disease before birth, there’s a lot we need to know before we can even try this method to help human fetuses. The Verge spoke to New York University bioethicist Arthur Caplan about this trial, the challenges of gene therapy, and why ethics boards will want to take a very close look.
This interview has been lightly edited for clarity.
This Nature Medicine study was in mice, but, of course, everyone wants to know about the human application. In your opinion, how far away is fetal gene therapy in humans? Are we talking a decade? Two decades?
I would say 10 years. Prenatal gene therapy is not a new idea. It’s been a long-standing dream of many people working with gene therapy to deliver the repair before cells get damaged.
Do you think that approval or adoption of prenatal gene therapy will be controversial? I know with CRISPR, there’s a lot of fear around the ethics of “designer babies.”
It’s a different discussion than designer babies when you have an embryo already under development, like here. Most gene therapy is intended to replace something that’s missing, thereby causing the chemistry to be “normal.” You’re usually not trying to improve or enhance when it’s already in utero. For that, it’d be easier to make an embryo in a dish and try to manipulate it there. Prenatal gene therapy is really going to be focused on preventing early damage from diseases.
And gene therapy is powerful for use in utero because it’s better used as prevention than for trying to repair things that have been damaged for many years. Clearly, some parts of the body regenerate, like the liver, but other parts, like the brain and heart, much less so. If they get damaged, you’re going to have a really hard time doing anything about it unless you get there early.
I don’t think it’s going to be controversial if the basic science and in vivo science is established. I think people will get the basic idea that it’s better to try to manipulate early than try to repair something when it may be too late.
Is it safer than something like CRISPR?
I would say no, not yet. It’s not accepted that one is safer. Everyone’s got their favorite, and CRISPR techniques are still being refined, too.
What about the downsides of the prenatal approach?
One is that you get a third person involved in terms of the risk of research: the mom. Trying to administer gene therapy around her can put somebody at risk. And until we’re really sure from many more studies, we can’t put moms at risk even if it would help the fetus. We still don’t know accurate it would be. You’re targeting particular systems to put in repairs, and there could be inaccuracies and cause in utero disasters. And we’re still not quite sure about how the exchange between fetus and mother works. We know that DNA is circling around to some extent, but is there going to be an immunological rejection?
What are the considerations we need to think about before this becomes viable?
One is cost. In utero is never cheap. It takes a lot of skill and technology to deliver things when you want them, and we have to be thoughtful about that. You may want to restrict who can try in utero work to doctors who have done those interventions before. Maybe they should be the first to do this line of work. It’s not just something that anybody ought to be allowed to do.
You’ll need close review by ethics committees because if you ask moms, if they’re willing to take a risk to help their child, most moms are probably going to say “yeah.” But they may not be able to process the risk or understand the dangers well.
How big are the risks? Are we talking on the scale of possible death?
I’m going to say death is possible, but what likelihood, we don’t know. People have had very bad reactions to gene therapy over the years. And now, there are two people exposed — well, one potential person and a real person.
We’re just not sure about the probabilities, and there are so many unknowns. So you need to have experimentation committees really give a long, hard look, more than you might for other procedures where if the patient said “yeah, I’ll do it,” you might yield to their ability to manage the risk and benefit. You don’t have that with fetuses, and you don’t have that with moms who really want to help and love their potential child.