I’m sure you know that I believe gene/cell therapy is the future of medicine, and one of the challenges for rare disorders like chronic hypophosphatemia will be justifying the substantial cost of development when the potential market is so small. (Same challenge as for prior forms of treatment really.) Fortunately, we’re in the early stages of this new phase of medical interventions, and we know where a hands-off approach takes us (no treatment for something in excess of ninety percent — yes, ninety, not a typo — of rare disorders). We need to start planning now, rather than sitting back and waiting to see what comes out of a random scramble among scientists working independently and competitively, rather than collaboratively.
At present, competition is rewarded, but there’s something of a transition to collaboration happening among the policy makers. I’m sure similar collaborative projects are underway in other countries/regions, but the one I’m most familiar with is in the U.S., where the NIH, the FDA, 10 pharmaceutical companies, and several non-profit organizations worked together to form the Bespoke Gene Therapy Consortium (BGTC). As explained by the former director of the NIH, “The goal of the Consortium is to reduce the cost of gene therapy protocols and increase the likelihood of success, making it more attractive for companies to invest in rare diseases and bring treatments to patients who desperately need them.” In other words, they’re encouraging collaboration and investigating treatments that might help a group of related disorders together instead of one by one.
With gene therapy (unlike “small molecule” or drug therapy), it makes sense that all disorders affected by a given gene can potentially share a treatment. In that case, it makes sense for all the disorders to be included in a single clinical trial, to make it easier to recruit volunteers (multiple communities means a larger number of patients to recruit from), and reduce the per capita cost.
It’s an obvious move, but it requires a change in thinking for researchers, since it goes against past practice, where there were incentives for pharmaceutical companies to divide the market into smaller pieces. That’s why the XLH community ended up with a treatment that could, in theory, work for some of the autosomal hypophosphatemia patients, but they were excluded from the XLH clinical trials, and are too few in number to justify a separate clinical trial. It’s also why there were separate burosumab trials for XLH and TIO, when in theory, the treatment targets the same thing (escessive FGF23), and the gene therapy that works for XLH could, in theory, also work for TIO patients.
And if all of this still sounds like gobbledegook to you, I totally understand. I’m still feeling my way through the maze of language and concepts. The American Society for Gene and Cell Therapy has a short and basic introduction to gene editing here. It’s intended to be understood by non-scientists, with definitions that don’t send you down a rabbit hole of needing definitions for the definitions. I highly recommend reading it, and don’t worry if the concepts remain a bit fuzzy. They will become clearer with each additional exposure to the information. I’ll share more resources as I find them, since sometimes a slightly different way of explaining complicated concepts can help cut through the fog.
Meanwhile, here’s a hint for reading scientific articles that get too detailed for you. There’s a famous quote from science fiction author Arthur C. Clarke, who said, “Any sufficiently advanced technology is indistiguishable from magic.” So, when the science gets too advanced for you, just tell yourself that that’s where “magic happens,” and move on. There won’t be a quiz at the end or any dire consequences if you don’t understand every detail, so just get what you can from the article, and let go of the rest, attributing it to magic. You’ll probably find that if you set the article aside and then come back another time to read it again, or you read a similar article with a slightly different take on the subject, you’ll understand a little bit more, with less material that has to be considered “magic.”
I started out thinking everything about XLH treatment was magic, and look where I am now, talking about monoclonal antibodies and gene therapy!
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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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