1229 replies to this topic

[resveratrol_guy]

Mobile phones can cause brain cancer and Alzheimer's anyway

 

Cell phone radiation is associated with a fourfold increase in acoustic neuroma (a form of brain cancer) among heavy users. But it's not even worth citing the study because the baseline odds are like 1 in 100,000. Alzheimer's is a theoretical risk based on periodically enhancing the permeability of the BBB; I suspect the risk is increased, and is more of a serious concern than cancer simply on account of the much higher baseline risk.

 

While we're on the topic, wired headsets do virtually nothing to solve the problem because they act as waveguides, delivering the microwaves directly to your ear drums. Only acoustic headsets are effective at blocking radiation, for example those made by rfsafe.com .

[Logic]

Looks like reason also posted the low-dose lithium study here. But it's a nonstarter: "Higher doses reduced lifespan but lower doses prolonged life". How would we have any confidence whatsoever that the human equivalent dose were appropriately "low"? BTW if I recall, lithium upregulates autophagy when delivered at the right dose; I'm not sure if that involves GSK3B.

 

I don't know if I agree that alternating periods of fasting and eating a full-calorie healthy diet is actually superior to continually fasting. There's a lot of evidence on both sides of the issue. In any event you're clearly correct that homeostasis is a big problem when it comes to sustaining the effect of any intervention, be it a drug or a lifestyle change. Personally, I think that slow-and-steady wins the race. I expect to make up for the homeostasis calibration by a lack of systemic stress due to constantly changing interventions. (Having said that, my last couple years has been nothing other than the latter!)

 

IIRC the japanese who were living longer due to the Lithium in their water supply got about 1mg of lithium per day, so thats a good starting point..?

 

You may be interestd in the Lithium, Pterostilbene, IP3 and circadian rhythm info here:

http://www.longecity...e-3#entry766445

[ceridwen]

Bioviva seems to want to alter glial cells as a potential Alzheimer's cure but I was searching for more information about glial cells when I read an article that was mostly about changing the behaviour of glial cells by supplementation not gene therapy. This seems to be a much less expensive way of achieving the desired result. The article was aimed at people suffering from ME and CFS so this would impact more people than those with AD.


Factors that switch off microglial neuroprotective mode and switch to Neurodestructive mode.
Oxidative stress and lack of Nrf2.
Taking Nrf2 activators May switch microglia to the neuroprotective mode.
Genisten,sulphoraphane and artesunate activate Nrf2 and there are Nrf2 activator supplements like this xymogen Nrf2 activator.
Apocynin also called acetovanillone from the herb Pichorzia Kurroa has been shown to promote the Neuro protective mode.

Inhibiting microglia might be a good strategy and cytokines.

Valcyte and cytovene potently inhibit microglia as do
Low dose Naltrexone
Hyaluronic Acid
Lithium
Ar-turnerone
Vitamin E
Wogonin flavonoid from skullcap
Baicalein
Silymarin
Genistein
Tetracyclines
Minocyclin
Blue berries
Sulforaphene
Acupuncture
N-acetylcholine-glucosamine
Sesame Seed Oil
Andrographolide
Acetate from vinegar inhibits microglia in Lyme Disease
Canabidol Cibdex and Dew Drops Hemp oil
Detromethorphan cough suppressant
Siberian Ginsing
Panax Ginsing
Gastrodia Elata
Isdojaponin D
Tetrandine Han Fang Ji
Risperidone
Terminalia Chebula Indian Herb
Memantine also blocks NDMA receptors
PEA
Astrocyte derived GDNF
Rehmannia

[Ark]

http://www.pbs.org/w...lzheimers-cure/

[Alex_G]

http://www.pbs.org/w...lzheimers-cure/

 

This looks really interesting. It looks like it might in a broad sense work in a similar method to Nilotinib. Also M13 shouldn't be too hard to get a hold of. I'm not sure why NeuroPhage doesn't just use M13 but decided to make NPT088.. Also they mentioned that intranasal delivery didn't make sense, but that's what was used in animal trials, it seems that is an easy delivery mechanism to me.

 

Thoughts?

[mag1]

Looks like we have another BBB issue with the phage.

 

Hmm, NPT088 and Lexiscan?

Safer and more effective?

[albedo]

Different Brain Regions are Infected with Fungi in Alzheimer’s Disease

http://www.nature.co...icles/srep15015

 

"The possibility that Alzheimer’s disease (AD) has a microbial aetiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae. Fungal material can be detected both intra- and extracellularly using specific antibodies against several fungi. Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi. Fungal infection is also observed in blood vessels, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals."

[ceridwen]

So how can the fungal infection be removed?

[resveratrol_guy]

I think the fungal infections are a very late stage form of pathology. The lack of immune competency is probably permitting them to occur. It seems grossly improbable, by comparison, they are the cause of the disease, or even that treating them would result in much clinical improvement.

 

But I don't think the studies bringing them to light are useless. They serve as yet more proof that the immune system, and in particular the microglia, are severely impaired in Alzheimer's. This goes back to ceridwen's point above about BioViva and their strategy of microglia rejuvenation via TERT.

[albedo]

So how can the fungal infection be removed?

 

I agreed with the point resveratrol_guy is making but if you know infection is there you would need an effective and as less toxic as you can method to remove fungi. There is a full literature on strategies for BBB drug delivery systems and a particular drug such as itraconazole has been studies. I did not look in detail but this might give a path:

 

Formulation and delivery of itraconazole to the brain using a nanolipid carrier system

http://www.ncbi.nlm....les/PMC4014385/

[albedo]

A good reminder (between others) from the National Institute of Aging (NIA) on resveratrol:

 

"Resveratrol, a compound found in red grapes as well as supplements, appears to have properties that may help protect the brain. Observational studies have shown that moderate consumption of red wine is associated with a lower incidence of Alzheimer’s disease, and animal studies have shown that resveratrol can reduce beta-amyloid deposits in the brain. Resveratrol also appears to affect the biological processes of aging-related diseases, including Alzheimer’s. An NIA-supported clinical trial will test the effects of resveratrol in people with Alzheimer’s disease."

https://www.nia.nih....tion-strategies

 

And this paper discusses resveratrol's (and analogs) BBB permeability and bioavailability:

Neuroprotective effects of resveratrol in Alzheimer disease pathology

 

 

Edited by albedo, 17 April 2016 - 09:44 AM.

[ceridwen]

Unfortunately I already have most of the symptoms listed as side effects of intraconazole so taking it would probably make those symptoms worse.

[Der Springende Punkt]

 

So how can the fungal infection be removed?

 

I agreed with the point resveratrol_guy is making but if you know infection is there you would need an effective and as less toxic as you can method to remove fungi. There is a full literature on strategies for BBB drug delivery systems and a particular drug such as itraconazole has been studies. I did not look in detail but this might give a path:

 

Formulation and delivery of itraconazole to the brain using a nanolipid carrier system

http://www.ncbi.nlm....les/PMC4014385/

 

 

Fluconazole crosses the BBB and is used to treat Cryptococcal Meningitis.
 

[ceridwen]

I have some of those too

[aaCharley]

The ever sensational Daily Mail has a report on reversing Alzheimer's in one week.  Treatment is with a protein designated as Il-33.

 

I don't know exactly why I cannot paste a link to the article reporting on the work of Glasgow University researchers.  It appears that they hope to test on humans this year.  Let's hope this one actually works.

 

BTW, If anyone has advice on the method I need to follow to make "copy - paste" work on this forum I would like to read it.  I'm just using IE-9 and the function works fine on other websites.

[resveratrol_guy]

The ever sensational Daily Mail has a report on reversing Alzheimer's in one week.  Treatment is with a protein designated as Il-33.

 

I don't know exactly why I cannot paste a link to the article reporting on the work of Glasgow University researchers.  It appears that they hope to test on humans this year.  Let's hope this one actually works.

 

BTW, If anyone has advice on the method I need to follow to make "copy - paste" work on this forum I would like to read it.  I'm just using IE-9 and the function works fine on other websites.

 

Here is the summary at the NHS (official UK health service) and the scientific paper. IL-33 is interleukin 33, which apparently activates the microglia into action, motivating them to clear accumulated plaque.

 

If this translates to humans, it might well be even more effective than hippocampally localized TERT therapy, which would make it the most significant Alzheimer's discovery of all time, and surely worth a Nobel Prize. I'm not holding my breath because it seems certain that nothing will happen in humans for at least 5 years, but everybody should "like" your post for bringing this to us.

 

This would be a pivotal group buy, for those with the courage and clincal justification.

[Alex_G]

as long as it didn't have adverse affects, I would be in for a group buy.

[aaCharley]

Thanks for posting those links as they are very good ones.

 

Some pretty amazing research being done.  Of course we should hope for more discoveries as there are more people involved than ever before and using methods that were not conceived of just a few years ago.  If the IL-33 treatment is effective it will sure increase the payoff for living a healthy life to live longer.  Alzheimer's has seemed to be a really random occurrence without a known cause.  If the brain microbe infection theory holds up, and this works out, it sure will be an amazing advancement in a short time.  Get an injection once a year, starting at maybe 30, and become smarter.

[pleb]

I have the article here. It was the daily express but which paper is of no consequence. it mentions an injection every day then after a certain length of time reduced to once a week. Whilst most are sensational many are worth reading and following up.
It mentions that IL-33 found naturally in the brain but reduces as we age is believed to turn on immune cells in the brain.
and increases the enzyme neprilysin which degrades soluble amyloid.
Trails are expected to start later this year
It was a similar article on the baati rat study in a newspaper where I first read about C60.

[albedo]

 

Transdermal implant releases antibodies to trigger immune system to clear Alzheimer’s plaques

Test with mice over 39 weeks showed dramatic reduction of amyloid beta plaque load in the brain and reduced phosphorylation of the protein tau, two signs of Alzheimer's

 

and the published paper by EPFL:

 

A subcutaneous cellular implant for passive immunization against amyloid-β reduces brain amyloid and tau pathologies

http://brain.oxfordj...06/brain.aww036

 

 

An implant to prevent Alzheimer's

http://actu.epfl.ch/...-alzheimer-s-2/

[mag1]

The gene editing revolution approaches!

When will we simply give up trying to understand biology and just change it?

We could save a ton of frustration and endless research budgets that has gotten us almost nowhere.

 

The CRISPR / gene editing technologies that are quickly approaching will allow us

to go directly to cures.

 

http://www.nature.co...ature17946.html

 

One of the only things that is holding things back now is a more vigorous sociopolitical movement

that firmly embraces the immortalitist perspective and is willing to pursue a more inclusive Right to Try

Law. It no longer seems beyond the realm of possibility (even with current technology) that someone of advanced

age with severe dementia and considerable financial means might gene edit their way out of the nursing home

and back to life- a possibly very prolonged one at that. 

 

The future has already arrived.

Members of the forum who are believers in the immortalitist philosophy should be pressing the agenda.

Edited by mag1, 21 April 2016 - 09:14 PM.

[platypus]

The gene editing revolution approaches!

When will we simply give up trying to understand biology and just change it?

Yeah, right, what could possibly go wrong??

[pleb]

Mag before you change it you need to understand it. Before changing it Every person needs his genome mapping and the correct sequence identified first.
They are still having trouble correcting problems in mice where they already know the sequence and what needs changing using CRISPR/Cas6 which is at the cutting edge of the technology.

[resveratrol_guy]

Between IL-33, nilotinib, intranasal betaNGF, and TERT therapy, I would wager that we can cure mild cognitive impairment or perhaps even moderate Alzheimer's, and perhaps just with 3 of 4 of those.

 

Furthermore, hippocampal TERT therapy might be unnecessary; systemic AAV transfection might suffice, if the animal studies are any clue, at least in the early stages of neurodegeneration. Speaking of which, did you read the news?

[resveratrol_guy]

as long as it didn't have adverse affects, I would be in for a group buy.

 

Unnecessary. You can simply buy human IL-33 for yourself here.

 

You could look up the dose used in the study, and use conservative ratios to extrapolate an appropriate human dose. Then you could inject it in the same manner as in the rodents. And then, of course, you would be stark raving mad to become patient zero for this obscure immune signalling molecule, but it just might work if you did it often enough.
 

[platypus]

 

as long as it didn't have adverse affects, I would be in for a group buy.

 

Unnecessary. You can simply buy human IL-33 for yourself here.

Only 7.5 billion € per kilogram! 

[resveratrol_guy]

 

 

as long as it didn't have adverse affects, I would be in for a group buy.

 

Unnecessary. You can simply buy human IL-33 for yourself here.

Only 7.5 billion € per kilogram! 

 

The price is comparable to betaNGF, which has noticeable effects at around 1 ug for an adult. So how much IL-33 do we actually need? Someone might want to dig into the study and offer an estimate.
 

[mag1]

What I am excited about is that we are now moving to a time where some disease X (where X is any genetic disease,possibly would not even need to be genetic) with some mutation Y could be cured with

CRISPR or other technology without a need to understand whatever X might be. Gene editing becomes a perfect black box in which all the complex

details surrounding the pathology of a disease are no longer relevant.

 

After over a century of Alzheimer's research, with two pathological accumulations (that were noted a century ago), we are still mired in considerable confusion.

The main thrust of the AD research has focused on amyloid, though it is very unclear whether clearing amyloid after disease progression will actually be helpful.

If we allow endless biochemical research to continue it might be centuries before cures emerge. Biology is hopelessly convoluted. Gene editing allows us to

side step all of this.

 

The report I cited above has advanced the field into what they call base editing (instead of gene editing). CRISPR technology is now roaring ahead.

It will be very interesting to see at what point pharmaceutical companies give up on the traditional research approach.

Billions of dollars have already been invested in AD research. Some of the pharmas are threatening (again) to leave dementia research because of the

near 0 success that has been achieved over the last few decades. With CRISPR / base editing one hammer will drive every nail, and the payback 

will simply startling. The pharmaceutical industry soon will not have to receive charitable contributions to actually make money.

 

 

This one might be worth a group buy: probably would not cost 10 gabillion € per kilogram. 

A family member with severe dementia tried the Cervarix vaccine with the MPL A.

 

https://www.scienced...30115143852.htm

http://www.pnas.org/...110/5/1941.full

http://ca.gsk.com/me...80/cervarix.pdf

 

Here is some recent research.

http://www.ncbi.nlm....pubmed/27079716

 

 

     

Edited by mag1, 23 April 2016 - 07:43 PM.

[Arisia]

It's interesting that LPS(lipopolysaccharide) is one of the mechanisms used by Alzheimer's researchers to induce inflammation in the brain,

[mag1]

Yeah, Logic posted on  lipopolysaccharide  on page 24. Dayglow bolded and underlined: He got four upratings for that!

Why do only the popular kids always get away with things! I want to be popular too.

 

MPL A appears to be a very powerful adjuvant and so the FDA is being very cautious.

There have been rare occurrences of auto-immune responses to it.

Strangely, one report noted that there was an over 12 times increase in narcolepsy in those receiving an MPL A. (?)

Those at risk have an identified risk genotype. 

 

Probably with the anti-AD effect, it is more that the MPL A creates a short term powerful anti-amyloid effect and

then the inflammation subsides.

 

 

I have been looking up where to get dosed up with MPL A.

All I am seeing is Ceravrix in the US.

Europe has the hepatitis B vaccine Fendrix and there is the allergy vaccine Pollinex Quattro.

 

 

 

http://www.enzolifes...c-ready-to-use/

 

Edited by mag1, 23 April 2016 - 09:10 PM.