We generally focus on the kidneys’ role in XLH, but today’s discussion is about the role of the liver in gene editing, which as I believe I’ve mentioned before, is the future, not just for XLH and other genetic hypophosphatemias, but for all of medicine.
Now, you’d think that gene editing for XLH would involve the kidneys, since that’s where the phosphate wasting occurs. Or possibly the bones, since that’s where the excessive FGF23 occurs. The problem with both of those options is that, from what I understand, it’s harder (verging on impossible with current technology) to turn OFF the overproduction of something (like FGF23 for us), than it it is to turn ON a few select cells to replace something that’s not being produced in sufficient quantities.
So, what the XLH researchers did instead was to look for a way to turn on something that would combat the excessive FGF23. Essentially, they created something similar to burosumab, an antibody that shuts down the excess FGF23, and then they needed to figure out how to get it to the FGF23 hanging out in the kidneys. In the early research, working with mice, not humans, they started with the liver, and used gene editing to cause the liver to produce the antibody, which would then travel to the kidney and block some of the FGF23 there.
That’s kind of where my understanding of the process ends. This article, Why is the liver a popular target for therapeutic genome editing?, is better than I could ever be at explaining why the researchers chose the liver and how things work from there. It’s written to be accessible to the non-scientist, and I highly recommend checking it out. The bottom line is that a lot of gene editing targets the liver, even if the ultimate process being affected (like blocking FGF23) doesn’t happen there.
There will be more information about the XLH gene editing research at the XLH Symposium in Edinburgh this summer, sponsored by the International XLH Alliance, so make sure your (or your kids’) clinician knows about it, especially if they’re already attending the International Conference on Children’s Bone Health, which starts the day after the Symposium.
I know that gene editing is complicated and maybe a bit scary or overwhelming to consider. Application of the science still a ways off for most disorders, including XLH, but it’s important to start getting familiar with the basic concepts now. Once the ball really gets rolling in the next couple of years, things are likely to move fast, and there will be a great deal of information for you to absorb, possibly with little time for reflection. You may need to make relatively quick decisions about clinical trials or treatments for yourself or a loved one, and it will take time to really get a handle on what’s involved. You can get a head start now by becoming familiar with the basics, like definitions and terminology (like the information in the linked article above about the liver’s role in gene editing). If you start now, investing just small amounts of time to read a manageable chunk of information, letting it sink in until you’re comfortable with it, and the moving on to a new manageable chunk, it won’t be quite so overwhelming later.
I’m still a novice when it comes to understanding gene therapy and its terminology, so you can learn along with me, as I share what I’m reading over the coming months. I hope you’ll let me know (email me Gin at GinJones dot com) if you have questions about gene therapy. I probably won’t have the answers myself, but I’m good at finding answers, so I’ll work on finding a resource that has answers for us all!
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Please note that the author is a well-read patient, not a doctor, and is not offering medical or legal advice.
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