Sometimes I get a little too full of myself (okay, settle down; you don’t have to be that emphatic in agreeing with me) and think I know all there is to know about XLH, from the inside out (except for the advanced organic chemistry).
And then I read something that makes me realize that I know NOTHING, but then again, neither do scientists, when their current knowledge is compared to what remains to be learned.
Today I learned that FGF23 can be produced by cells OTHER THAN bone cells! According to a new article titled “High fat diet induces gastric production of FGF23,” in some circumstances, “organs other than bone can produce FGF23, including kidney, heart, liver, and lung.” Plus, as the title states, even stomach cells can produce FGF23!
Which makes me wonder if we know, for sure, that the excess production of FGF23 in XLH is actually coming from bone cells or somewhere else, and how we could find out for sure. Is it possible that our bones are just producing a normal amount of FGF23, but some other organ is producing amounts that it wouldn’t in a non-XLHer, so that the total is excessive? Doesn’t seem impossible (to layperson me), especially given that not all XLH patients have high FGF23 levels in blood tests (or don’t have consistently high levels), and yet we all clearly have too much FGF23 going rogue in our kidneys.
That seems like an important question to resolve, because the holy grail for XLH research today is figuring out what the pathway is between the known genetic mutation(s) and the cells that produce too much FGF23. We need to understand that early pathway in order to produce a cure that could permanently target that earlier pathway than the one we know about AFTER the FGF23 is produced and then is temporarily intercepted by burosumab in the kidneys.
This is much more advanced science than I have the expertise to parse, but I have to wonder whether learning that our excessive FGF23 comes from a source other than the bones might be a breakthrough in the search for our holy grail. Alternatively, if we learned that it’s solely from bone cells, well, that rules out the other possibilities, so we would know that research focused on the bone cells is looking at the right path endpoint.
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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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