My mom is on one of the experimental groups of meds for placque reduction, and has been for about 3 years. She has stopped deteriorating as rapidly as she had been - though she has deteriorated in the past 3 years. We are thinking that she has about another year to year and a half until we need to place her into a facility, as my brother works full time and is currently living with her to keep her in the family home. [mrAru and I live 400 miles away, and if we lived locally I would not be able to physically take care of her if she was any worse. About all I could realistically do is make sure she takes her meds and eats … which my brother manages quite well.]
I have to worry about alzheimers from her side of the family and parkinsons from dads … sigh
Well, often it seems random. And then you look back and see the risk factors that you did not notice.
Actually, Huntington’s is a weird one. Not as clear-cut as you’d think. I once got a Huntington’s test done, thinking it was going to be one of those simple “let’s look for the gene, and if it’s not there, yay!” kind of thing. The report I got back was an education for me. Huntington’s isn’t caused by a codon point mutation (my simplistic view of a mutation), but is actually caused by a whole bunch of nucleotide repetitions at a locus. This gene is especially susceptible to mutations–genes aren’t equally vunerable to being altered through the generations! This was news to me and I have a Ph.D in biology! So in one generation, a person can have a high number of mutations at this gene and yet not develop Huntington’s, but in the next generation (or the one following), it pops up in the kids or grandkids because the number of repeats have increased to a certain tipping point. So you can be a carrier for Huntington’s without having the family history to warn you.
The report I got back said that I will not develop Huntington’s (whew!), but that I should have genetic counseling done because any grandchildren/great-grandchildren I have might. Apparently I have a higher than “normal” number of repeats in my huntinton gene. As I don’t plan on having any kids, this news immediately didn’t keep me up at night. But I do have nieces. Should they know about this? I haven’t told them.
What I want to know is the role epigenetics plays on the mutability of that gene. If I were to have kids, it would probably be too late to do anything about mutations they inherit. But would it be too late for them to protect the gene their progeny inherits? Or has epigenetics already determined the destiny of my entire lineage?
Lane, I am on an Institutional Review Board at a large medical center. My task as a voting member of that board is to review studies done on humans for safety, ethics, etc. I can say without hesitation that I frequently see studies being done using nutritional supplements of various kinds as potential treatments for various diseases, including Alzheimer’s. These studies are funded by individual departments, philanthropic grants, government funds (NIH, etc.) and even pharmaceutical companies. I know nothing about the particular line of research you’re discussing, but I think you are oversimplifying matters when you assert that almost no one is interested in a non-pharmaceutical solution - especially because any company with an ounce of sense would immediately create and patent a custom blend of the ingredients in question and market the hell out of it. There are plenty of plant-based pharmaceuticals out there.
Alzheimer’s Disease research is definitely one of the most disappointing research areas. If any one of those “remedies” mentioned by Lane Simpson had a chance in hell of working, the drug companies would be all over it. There is absolutely nothing preventing Pfizer from patenting an FDA approved grape seed extract for the treatment of Alzheimer’s. In fact, that would be ideal, since drug synthesis is extremely expensive. The profit margins would be astronomical.
Here is one group of researchers that attempt to make a link between [HTML=http://www.news-medical.net/news/20111018/HSV1-drugs-could-slow-progression-of-Alzheimers-disease.aspx]Alzheimer’s Disease and Herpes Simplex 1
. I have no idea if there is a connection. Here is [HTML=http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2011120a.html]another paper
that demonstrates Alzheimer’s can be transfered between animals (admittedly, not in any way that demonstrates it is contagious.). I think a large portion of research indicates that it behaves like a prion.
“An’ we must stop it in our lifetime, 'fore it kills somebody!”
Sorry! Couldn’t help myself behaving like a prion.
The above is only some comic relief, okay, guys and ladies?
But see? That’s the answer to the OP’s question, and something I have addressed many times in the blog. There’s such a wealth of mostly useless information, that no one can agree on anything. Especially those folks who are in the labs.
Oh I think the guys in the labs are in complete agreement that we know absolutely nothing, and will try anything at this point. The failure of the gamma secretes inhibitors, pretty much puts the most promising avenue of research back at the starting point. If the obvious conclusion is correct, then the amyloids aren’t the cause disease, they are an effect of the disease not related to dementia.
I am having troubles posting this message, perhaps because previous versions were too long. I will try to be more succinct this time. The points made by WarmNPrickly and Ferret Herder do not preclude the possibility that peroxynitrite scavengers are an effective treatment for Alzheimer’s disease. The patent process is more complicated than either suggests. First, the FDA does not approve nutritional supplements (which may be part of the problem), second products of nature cannot be patented (such as essential oils in their natural form), third you cannot patent something that has already been patented (such as the case with one form of grape seed extract), and fourth you cannot patent something that is off patent (such as minocycline). You can develop a blend of natural ingredients (as Ferret Herder suggests) or develop a new extraction process but the product would have to be more effective than the natural ingredients sold separately or the existing extracts. So far the researchers working on peroxynitrite scavengers have not succeeded in doing so. Unless such a product can be developed, pharmaceutical companies are not going to promote a treatment that is more effective than current medicines, but over which they have no control (most essential oils can be purchased for around ten dollars a bottle). There is considerable evidence that peroxynitrite scavengers can be used to treat Alzheimer’s disease, it is just not the answer that most members of the Alzheimer’s reseach community are seeking.
AD has struck close to home so I have had a lot of conversations with doctors and neurologists recently. One thing they uniformly say is that we should all be taking Omega-3 fatty acid supplements daily.
That’s not to say that is the only thing that will delay the onset but it is one cheap, easy thing to do.
Do you have a cite to an article in a reputable peer-reviewed medical journal that supports your claims that “There is considerable evidence that peroxynitrite scavengers can be used to treat Alzheimer’s disease” ?
I have many artricles from peer-reviewed medical journals on the use of peroxynitrite scavengers to treat Alzheimer’s disease but I will just cite a few here and provide google searches for some others on a separate post:
T. Alkam et al. A natural scavenger of peroxynitrites, rosmarinic acid, protects against memory impairment of memory induced by AB25-35. Behav Br Res 180 (2007): 139-45.
D. Jimbo et al. The effect of aromatherapy on patients with Alzheimer’s disease. Psychogeriatrics 9 (2009): 173-9.
S. Akhondzadeh et al. Melissa oficinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomised, placebo controlled trial. J Neurol Neruosurg Psychiatry 74(2003): 863-6.
S. Akhondzadeh et al. Salvia oficinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind randomised and placebo-controlled trial. J Clin Pharm Ther 28(2003): 53-9.
M.A. Smith et al. Widespread peroxynitrite-mediated damage in Alzheimer’s disease. J Neurosci 17 (1997): 2653-7.
A. Frydam-Marom et al. Orally administered cinnamon corrects cognitive impairment in Alzheimer’s disease animal models. PLoS One 6 (2011): e16584
D.W. Peterson et al. Cinnamon extract inhibits tau aggregation associated with Alzheimer’s disease in vitro. J Alzheimer’s Dis 17(2009): 585-97.
S. Jeon et al. SuHexiang Wan essential oil alleviates amyloid beta induced memory impairment through inhibition of tau protein phoshphorylation in mice. Am J Clin Med 39
(2011): 917-32.
I have several other articles showing the effectiveness of peroxynitrite scavengers such as minocycline, grape seed extract, holy basil (Ocimum sanctum), and the alga Symphyocladia latiuscula in animal models of Alzheimer’s disease. In fact, every single peroxynitrite scavenger that has been used in animals or human beings has partially reversed Alzheimer’s disease.
First article is a post-mortem analysis of brain tissue, which provides some indicators that peroxynitrites may indeed be involved somehow in the Alzheimer’s process. Good preliminary info but not proof that introducing substances to fight these molecules will have a positive effect.
Second (btw, trying to look up this article online was annoying - their journal may be all “interactive” and crap, but it’s hard to find an article when you’re going by journal issue. And it’s “Frydman-Marom”) is an animal (flies, to be specific) model, which is good for preliminary research but not predictive of what will happen once tested in a human. It’s also very important to note that regardless of the title, cinnamon as we typically find it was not used. It was powdered cinnamon bark treated with potassium chloride, and also does not specify the exact species used; we use 4 different kinds of Cinnamomum plants in cooking, and they may well have different proportions of active ingredients - considering their flavors can vary greatly between the species, this would not surprise me at all. Interesting preliminary info especially since it was taken in orally, but no reason to start gobbling cinnamon in bulk unless you’re really in a bad place and willing to just try whatever, which I don’t blame.
Third (scroll down) has only the abstract online that I saw. Here at least they specify the species, and it’s an extract from Ceylon cinnamon, which is not the usual species commonly found in grocery stores. (That’s cassia/Chinese cinnamon.) The abstract doesn’t specify where the cells came from, and it’s an in vitro study so they’re not testing this on living subjects. I’ll assume human subjects since it doesn’t specify.
Fourth article - a mix of various herbs used in Chinese medicine (including an apparent cinnamon type) turned into an extract and injected directly into the hippocampus of mice.
So, what it boils down to is that these are all building blocks of possibly finding an effectiveness of oral intake of cinnamon extracts or other herbal-type extracts for treatment of Alzheimer’s. There is no proof in these articles that this is definitely effective in living humans as a treatment at this time. And I am not qualified to speak on whether inhalation of anything is effective as a treatment intended to pass the blood-brain barrier, though my wild guess would be no.
This isn’t proof that drug companies aren’t interested. They will be interested once there is more direct evidence that an oral or other easy-to-administer preparation has a significant effect in humans.
I’m not trying to be a nay-sayer. If we found an easy to procure source that could be purified into a highly effective drug, that would be marvelous. But even when initial studies have promise, it is not at all uncommon for things to just not work - or have horrible side effects - once you get to the point of testing them in humans.
I work in medical research - not with a pharmaceutical company, but at a hospital where we do the testing on volunteers end of things. We are thrilled to test whatever - we’ve done vitamin studies (some of which did work!), pharmaceutical drugs, devices, all kinds of stuff. My specific area is ophthalmology.
We participated in one study that had a ton of promise. It was a small start-up company that had a fabulous idea, to help restore vision to people with a disease that had no treatments. The disorder eventually blinded everyone who had it, over time, with nothing that would help other than iffy reports on whether certain vitamins might slow the process, so doctors would tell patients to just go for it on the vitamins and hope. Theoretical and animal models showed promise for this new treatment. An initial study of a small number now-pretty-much-blind volunteers had some promise, so they raised money and went for it. A very small number of hospitals in the US started recruiting people, including where I work, and there were a lot of people eager to participate.
It got crazy when an international radio show found out about the study and made this sound like it was a guaranteed miracle. I came into work the next day and our voicemail boxes were full. People from around the world were begging to get into the study, even though we’d closed recruitment.
I still get phone calls and E-mails now and then, even though the study closed years ago. With the somewhat expanded test group… there was no measurable improvement. The initial tests were only on maybe 10 people, and I suspect those who showed improvement in those were maybe so deeply in despair at the start that they just didn’t “try hard enough” to see hand motion or faint changes in light vs. darkness, and being in the study gave them enough hope to notice. (Trying is important in vision studies - this is why in later testing of different types of eye treatments, it’s helpful for both the study subject and the vision tester to not know whether the subject is receiving the study medication or a placebo, as they may be encouraged to try harder if on the medication.) The company went bankrupt, the ownership of the treatment was sold off and put on a shelf somewhere.
Even large drug companies that bet on too many bad picks may really hurt their chances of continuing to exist, and even drugs extracted from plants require tens or hundreds of millions of dollars to test properly, not to mention several years at a minimum.
So this shows promise, possibly. But please, if you’re desperate to try what seems like a low-risk treatment possibility, don’t spend gobs of money to get questionable “extracts” from fly-by-night companies. Try to at least do some research to make sure that you know exactly what you’re getting, and that you don’t spend much to do it. No sense in poisoning yourself with pills or droppers full of bad stuff or losing lots of money to scammers.
Quoted for truth. (And thanks for doing such a great paper-by-paper breakdown, I was thinking of doing the same and now I don’t have to :D)
Thing is, there are gobs of Very Exciting Preliminary Results that never lead anywhere productive. I’ve worked in a lab that’s made some of those results, showing how certain mechanisms affect Alzheimers pathogenesis in an animal model. But the vast majority just don’t pan out. The vast majority of treatments that works in cell culture or invertebrate models don’t work in mouse models. And that continues, so that the vast majority of effective treatments for mouse models don’t have the same effect in humans, or are accompanied by some unforeseen toxic effect.
So Lane has found a decent handful of preliminary research that links oxidative stress and Alzheimer’s disease. That’s promising, and definitely worth more investigation. But there’s nowhere near enough evidence to prove a causal relationship, and certainly not enough to have a treatment for humans.
And far stronger hypothesis have failed. Again, consider the gamma-secretase inhibitor case I mentioned before. A pubmed search of “gamma secretase alzheimers” pulls up nearly two thousand papers on the topic, over twenty years of research. That’s enough to convince the pharmacuetical companies to pursue clinical trials, and they did. But they failed spectacularly.
Thank you lazybratsche and Ferret Herder for your well-informed comments and caveats (and spelling correction). If you would like to do so, please also comment on the four studies listed above the ones which you responded to. The first, whose title should be “A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced AB25-35”, links peroxynitrites to short-term memory impairment and one peroxynitrite scavenger to protecting against this memory loss. The next three are small-scale, limited-time period trials with essential oils (tinctures in the Akhondzadeh trials and aromatherapy in the Jimbo trial). My main point is that not only have peroxynitrite scavengers been successful in mice and other models (which as both commentators note have limitations), they have also shown success in three (albeit limited) clinical trials (and in case studies, although I know scientists don’t like case studies). I will make some more comments on a separate post.
A few more comments on the use of aromatherapy in the treatment of Alzheimer’s disease. Phenolic compounds cross the blood-brain barrier and through aromatherapy directly reach the hippocampus–the part of the brain most affected by Alzheimer’s disease. The safest and probably the best form of cinnamon to use is Ceylon cinnamon (Cinnamomum zeylanicum) also known as true cinnamon (Cinnamomum verum). You can buy cinnamon leaf essential oil in this varieity. Cassia (Chinese) cinnamon contains a compound known as coumarin which can damage the liver in high doses. The compound in Ceylon cinnamon that scavenges peroxynitrites and possibly protects against and treats Alzheimer’s disease is eugnenol–a methoxphenol (see studies by Chericoni and Irie in regards to eugenol). Tinctures of essential oils are more difficult to use than aromatherapy because if they are not diluted properly they can cause liver or kidney damage. The possible contraindications for the use of aromatherapy include allergies (headaches and nausea), possibly increased risk for seizures in some people, coma (if smelled for long periods of time), a possible increase in blood pressure, and cancer (eugenol which is an antioxidant at extremely high levels of exposure can be an oxidant). Other than allergies, there appears to be very little risk from the intermittent use of essential oils via aromatherapy. I am not saying that the evidence that aromatherapy can be used to treat Alzheimer’s disease is irrefutable, I am just saying that evidence is very good.
Finally (for today at least), here is an explanation for why efforts to block the formation of amyloid plaques or to remove them have not been more successful. The pathway that leads to the formation of amyloid plaques (phospholipase C gamma or beta activation and the subsequent activation of protein kinase C and intracellular calcium release) is the same pathway that leads to the formation of peroxynitrites (the latter also involves the activation of tumor necrosis factor-alpha and its activation of nuclear factor kappa b). When you limit the activation of phospholipase C gamma with phenolic compounds or polyunsaturated fats (such as Omega 3-fatty acids in fish oil), you likely delay the onset of Alzheimer’s disease. But peroxynitrites apparently begin doing their damage to g proteins coupled to receptors involved in smell and short-term memory even before the the amyloid precursor protein is cleaved to form amyloid plaques. The plaques further contribute to peroxynitrite levels by elevating homocysteine levels (by entombing zinc) and by leading to higher levels of superoxides (by entombing copper and zinc–two elements necessary to active the superoxide dismutase which converts superoxides into hydrogen peroxides. Peroxynitrites are formed from the combination of superoxide anions and inducible nitric oxide both of which are a product of nuclear factor kappa b activation). So if you reduce the formation of amyloid plaques or somehow dissolve them, you lessen the progression of Alzheimer’s disease but you don’t reverse it. Peroxynitrite scavengers appear to do the latter.