Mark,MarkW wrote:Hello Guys,
I read this as theory not known facts. Does the gene CYP27B1 do this is all pwMS? To what degree? Is there evidence? Does D3 from sunlight need this gene? It would be great if a pulse of calcitrol then D3 reboots the MS immune system and keeps it operating normally. If the dose for a 70kg human (me) was a reasonable risk I would try this in the coming weeks. I need to study the paper and supporting papers in detail. We need to keep in mind that there is a D3 blood level/disease activity level relationship so there are more variables to consider. Like Ed says the costs of taking calcitrol/D3 is very low so funding research will be a problem.
While I appreciate what you are saying, I think it is fair to characterize Prof. Hayes' findings as facts, but facts limited at this point to EAE mice. She has conducted a series of three major studies of this leading to her latest paper which brings this all together.
CYP27B1 is the gene that expresses the protein that converts D3 to calcitriol in people, pwMS and mice. In pwMS, this gene is unable to do this in the CNS at the site of the inflammatory process associated with MS. The gene functions elsewhere in the body or we would have no calcitriol and MS would be the least of your worries. :>)
As far as EAE and considerable research related to pwMS, there is a lot of evidence and measurement of the effect of this in terms of the proliferation of CD4+ T-cells and the fact that a single, high dose of calcitriol is sufficient to set off apoptosis which kills them off. That, along with other beneficial effects of the calcitriol is enough to effectively reboot the immune system in the CNS. It stops the disease process and keeps it in remission.
The studies are conclusive in this regard. What is not known is whether this will work the same way in humans.
I have copies of a group of relevant papers which I can send anyone who doesn't have free access. PM me with an email addy and I'll send them to you. One is Prof Hayes Calcitriol + D3 study. The second is a study by the Ebers group on the long term use of calcitriol in pwMS. The final paper is a dose escalation study of calcitriol in pwCancer which may or may not be relevant to pwMS.
Based on calculation of the human equivalent of the calcitriol doses being given to the EAE mice, the proposed starting dose to test whether this will work in humans is 70% as much as the Maximum Tolerated Dose in pwCancer.
I have used calcitriol in cats for over 13 years and wouldn't hesitate to take a single dose of calcitriol at this level just to test the effects. And if I had MS, I wouldn't hesitate for a nanosecond to see if this works.
I am in discussion with 6 medical professionals who have MS to see if they will pioneer the use of calcitriol + D3 in humans to assess the safety and see if it moves the needle.
And I have discussed getting a formal clinical trial organized and funded to test this in a small, IRB-approved trial to again, see if it is safe and moves the needle on MS.
As these efforts become more finalized, I will keep everyone posted on them here.