Why are we not using HOPO to chelate gadolinium?
The primary reason we are not using HOPO to chelate gadolinium for this is that HOPO has not been FDA approved for use in humans for any treatment. In comparison, iv-DTPA is FDA approved for decorporation (AKA chelation) of actinide radioactive metals (most famous of which Plutonium), and using it for Gadolinium is off-label, but an accepted practice. Physician do this all the time, and it is customary practice. FDA approval requires 3 phases of research - which is time-consuming and can be quite expensive. Generally at least 3 years at a very minimum (usually 7 years), and anywhere from 100 million to 1 billion dollars (that's why in large part, proprietary drugs are so expensive). Fortunate few patients (fortunate, if HOPO is very good) can take part in all 3 phases of study, and I am not sure, but phase 1 could be starting soon > but phase 1 is very few patients (maybe 20).
As you know I often give a shout out to HOPO as something to look forward to in the future... but not to hang out hope for today. Oral DTPA is also fully developed, but similarly has not gone through the phases of study to bring FDA approval. I cannot say if HOPO will be FDA approved or in fact how good it will be, from the perspective of everything from bio-availability to efficacy. As a whole though, I like the ligands of GBCAs themselves, as accomplished scientists had explored many ligands in the 1980s to 1990s to see which ones will be effective to chelate Gd in a stable fashion and to minimize toxicity. At some point, and I have not yet, I will reach out to some of these scientists to ask them if they ever looked at HOPO as a ligand - and if not, why not.
I have deliberately kept at arms length from the HOPO folks, for one extremely critical reason, that benefits all GDD patients. For observations to be considered scientifically valid, they have to be reproducible by INDEPENDENT groups of physicians/scientists. So if everything that has to do with GDD in the peer-reviewed literature (the critical addition being correct science and beneficial to patients - and not defamatory work) has my name on it, then there would be no independent group to confirm that patients with normal kidneys get sick from gadolinium, and hence insurance companies could be justified in saying that the data is not generalized enough validated enough to accept the disease, and no ICD10 code. That is the primary reason I write so many blogs on what other physicians and scientists should do- even though I would love to have my name on the paper that describes the gene responsible for GDD, defining all the immune pathways involved, or the most definitive DMARD drug that treats GDD sufferers instantly to improve them, it is better for patients if someone else discovers them and writes it up, as the science is then generalized and validated by other independent groups.
The best thing for HOPO and for GDD patients if it turns out to work well, is for me to have nothing to do with it.
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