Posted 21 February 2015 - 07:32 AM
Phase 2 trial of methylene blue has finally been published! ( 8 years after the trial ended). AD was stabilized in mild to moderate patients for up to a year!
Articles explained why the high dose treatment arm did not respond as expected (appears to be a plausible explanation).
http://iospress.meta...ltext.pdf (open access)
http://www.ncbi.nlm....pubmed/25320049
Posted 23 February 2015 - 01:25 AM
All the tri-carriers of (HFE gene) C282Y, (TF gene) C2, and APOE 4 had AD or MCI.
Synergy between the C2 allele of transferrin and the C282Y allele of the haemochromatosis gene (HFE) as risk factors for developing Alzheimer’s disease. Journal of Medical Genetics, 41(4), 261–265.
C282Y and C2 risk of AD replicated in this study:
Alzheimer's Disease Neuroimaging Initiative. (2010). Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 153B(4), 955–959.
And here:
Transferrin and HFE genes interact in Alzheimer’s disease risk: the Epistasis Project. Neurobiology of Aging, 33(1), 202.e1–202.e13.
Further studied here:
Iron genes, iron load and risk of Alzheimer’s disease. Journal of Medical Genetics, 43(10), e52. doi: 10.1136/jmg.2006.040519
Posted 23 February 2015 - 01:31 AM
Posted 23 February 2015 - 05:23 PM
Posted 23 February 2015 - 05:35 PM
Iron may be a factor in dementia:
http://newsroom.uts....factor-dementia
That's not news, chelation therapy was in trial for AD and diabetes in 2009 or earlier and as far as I remember it wasn't especially effective.
Posted 23 February 2015 - 11:29 PM
"...We think it important to emphasize that the most effective clinical treatment yet devised for moderate- to late-stage AD patients was the implementation of the first generation anti-oxidant and trivalent iron/aluminum chelator desferrioxamine to attempt to remove aluminum from the brains of AD patients... . Second generation aluminum chelators such as Feralex-G, either alone or in combination with other chelators, has shown higher specificity, increased selectivity and higher efficacy in aluminum sequestration and chelation in preliminary in vitro studies "
Posted 23 February 2015 - 11:41 PM
I do not understand stabilization is not the same as not progressing.
Perhaps this means that the disease pathology could in various ways still be advancing even with stabilized cognitive function.
Could anyone help out here?
Posted 23 February 2015 - 11:48 PM
I'd like to make a comment about the state of my health now with early dementia. I used to give blood when I was well and it was always a toss up when it came to having my blood levels measured. I always seemed to be border line anemic. Border line anaemia could that be an early test for those who are going to develop Alzheimer's? I have a friend who experienced the same thing when giving blood but her health is good. She is taking Vitamin D probably very wise.We were never sure that we'd pass the blood test and be allowed to give blood.
You might be on to something. This is from the link that Logic posted above.
The results revealed, first, that compared to healthy volunteers, participants with Alzheimer's had lower levels of iron in their plasma, a condition linked with anaemia of unknown cause.
Intriguingly, results from the ICP-MS and SEC-ICP-MS tests, showed healthy and Alzheimer's participants had the same amount of transferrin in their blood but that the amount of iron carried by the transferrin was lower in Alzheimer's samples. The implication: transferrin isn't shuttling excess iron efficiently from the brain.
We need to look at the sequence of those transferrins; the transferrin SNP that mag1 just posted about is probably a key thing; of course the others are also important. M30 might be the answer for the transferrin flaw, since M30 is brain penetrant. Everyone should be getting their genome scanned for problem SNPs, because there are things that can be done to deal with them.
Posted 23 February 2015 - 11:58 PM
Exactly right about the idea that getting one's genome sequenced is good idea.
From the articles that I posted about C282Y and TF C2, there are a fair percentage of people walking around who might not have any history of AD in their family, though if they had some weird combination like that then they might be at high risk. Hopefully, within the next year or so there will be much greater clarity into such epistatic events.
This is all the more important as the articles cited noted that iron overload is a treatable condition (especially before the onset of overt AD).
Posted 24 February 2015 - 01:31 AM
All the tri-carriers of (HFE gene) C282Y, (TF gene) C2, and APOE 4 had AD or MCI.
Synergy between the C2 allele of transferrin and the C282Y allele of the haemochromatosis gene (HFE) as risk factors for developing Alzheimer’s disease. Journal of Medical Genetics, 41(4), 261–265.
C282Y and C2 risk of AD replicated in this study:
Alzheimer's Disease Neuroimaging Initiative. (2010). Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 153B(4), 955–959.
And here:
Transferrin and HFE genes interact in Alzheimer’s disease risk: the Epistasis Project. Neurobiology of Aging, 33(1), 202.e1–202.e13.
Further studied here:
Iron genes, iron load and risk of Alzheimer’s disease. Journal of Medical Genetics, 43(10), e52. doi: 10.1136/jmg.2006.040519
If you want to look at your own genome, here are the rs codes for the two transferrin alleles:
C2 = rs10492296 Risk variant is T
C282Y = rs1800562 Risk variant is A
At 23andMe, you can look up the individual rs codes in your data by selecting "browse raw data".
Posted 24 February 2015 - 01:59 AM
Thanks niner I am now getting depressed something has gone wrong today. I'm not sure what but I think I'm beginning to get depressed as well. I can't stand this cos like everyone here I don't want to die.
Sorry to hear that you are feeling poorly. I hope you feel better soon.
Where can I get M30?
I don't think you can buy it ready-made, but it's a relatively simple molecule, so it probably would not be terrifically expensive to have it synthesized. (probably several thousand USD, so not exactly cheap either) Professionals can get it from Sigma Aldrich, but only in milligram quantities (not enough for human therapy) and it's very expensive from them.
Posted 26 February 2015 - 01:14 PM
Posted 14 March 2015 - 02:23 AM
Thell beat you to it in this thread. But IMO it's better to have a redundant post than no post at all because people fear creating redundancy. So good on you for posting.
Anyway I've been chasing this one for a while since my friend alerted me. The media reports are rather misleading, I think. This is maybe the most accurate summary. In particular, the original science had to do with vibrating the BBB with ultrasound so as to enhance its permeability to drugs. By focussing the ultrasound beam(s) on a tiny volume of brain tissue, targetted drug delivery might thus be accomplished. Unfortunately, this required the use of inert particles to resonate with the ultrasound and bombard the BBB (and who knows how inert they really are). And of course it would not be possible for most of us to accomplish this, if for no other reason than a lack of those particles or a willingness to inject them. So this was nothing more than expensive mouse science destined for the scrap heap.
However, the real news in all this is that ultrasound alone appears to have massive disease-modifying prowess. In other words, we appear to have the beginnings of mechanical LLLT, as it were.
Unfortunately, the paper above is paywalled (it's only $20, if one of you experts wants to have a look). I'm personally not going to spring the cash, because I get the message: (1) ultrasound with the right frequency, duration, power, and localization probably annihilates brain plaque (perhaps via a hormetic pathway involving the microglia, as opposed to direct sonication) and (2) it will be decades before the FDA (dis)approves of this therapy for popular use. Therefore, it's time to repurpose that old Sonicaire toothbrush set that you bought at a garage sale as a multifocal ultrasound beam device, rather like the sonic equivalent of the gamma knife! For that matter, who cares about localization; zap the whole brain (uh... maybe)! Where's lostfalco...
Edited by resveratrol_guy, 14 March 2015 - 02:25 AM.
Posted 14 March 2015 - 02:34 AM
Glad to see someone picked up on my post. Internet sources are using hyperbolic language This is a Cure etc.. Wanted to see if anyone could tune into the story without the hype.
Science is so competitive. The study on the other thread was from Toronto research published in February.
The study I posted was from Australia from an article published in the last few days.
It must be very frustrating to be a scientist having to wait months (sometimes a year) to get research published while
others are aware of your research and rush the same study to print.
There is some question about the applicability of the ultrasound result to humans. Traditional ultrasounds apparently do not get through
the brain. Yet, some online reports claim that this is already possible.
http://in.mobile.reu...150311?irpc=932
Posted 14 March 2015 - 04:02 AM
There is some question about the applicability of the ultrasound result to humans. Traditional ultrasounds apparently do not get through
the brain. Yet, some online reports claim that this is already possible.
(I assume you had some other link in mind? Reports would indeed be interesting.)
It's definitely possible, especially given this famous TED talk and this update on MR-guided focussed ultrasound surgery. It seems to me to be a mere matter of optimization (which is hardly simple, but vastly simpler than tackling Alzheimer's biologically).
The question is, can we create a safe and effective homebrew version? Laughs aside, it just might work, if all we're really doing is annoying the microglia into cleaning up the mess. (I'm not entirely convinced that LLLT isn't doing just that. But whatever. It works.)
Posted 14 March 2015 - 04:18 AM
Yeah, that was the one. We had to get through some medical dogma first. The generally accepted view in medicine was that ultrasound to the brain would require brain surgery.
Looks like that dogma is going to have to change.
Could sure make things better for brain tumor patients!
It is going to be real tough for the AD community waiting 2 years while they rearrange the deck chairs for this one. There is a whole lot of people who will want to jump the
queue.
Edited by mag1, 14 March 2015 - 04:19 AM.
Posted 16 March 2015 - 02:53 PM
My concern with utilizing focused ultrasound to disrupt the BBB is the how well it heals. Breaking up the AB is great, having it cleared is great. But if the junctions are damaged to an even worse state what would the ramifications be?
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