RSS Feed Print
Axona
JAB
Posted: Sunday, December 4, 2011 11:08 AM
Joined: 11/30/2011
Posts: 740


OK, folks, just to inaugurate this forum ... Accera has announced that the FDA has accepted its application for a long-term (6 months double-blind placebo-controlled plus 6-month open label) Phase II/III clinical trial for "AC-1204" as an IND.

 

http://clinicaltrials.gov/ct2/show/NCT01211782

 

Axona, which is based on caprylic triglyceride, is sold as a prescription-only "medical food".  The testing that is required for a product to be sold as a "medical food" is quite limited in comparison with the testing that is needed for an IND (investigational new drug).  The data that has been developed to date appears very promising -- and many of us have reported that Axona is beneficial to our loved ones.

 

Because of the limited testing, many doctors are leery of recommending Axona.

 

Well, the active ingredient in AC-1204 is caprylic triglyceride.  I.e., we're going to have a chance to see just what Axona-by-another-name (possibly in a different formulation, couldn't find info on that) can really do!

 

Earlier studies indicated there may be a significant difference in the degree to which Axona can help patients with vs without the APOE4 allele.  This clinical trial (which is not yet open for recruitment, but which will be conducted in St Petersburg FL) will be limited exclusively to APOE4(-) Alzheimer's patients.


Diane D
Posted: Monday, December 5, 2011 12:44 PM
Joined: 12/5/2011
Posts: 1


Just joined forum but have had more experience dealing with Alzheimer patients than I care to think about.  My Grandmother developed Alzheimers many years ago and was enrolled in a research study which is probably what saved me mentally.  Now my mother has been diagnosed and I watch her slowly deteriorate.  It seems that each time she goes to her doctor he gives her something new.  Most recently Axona.  I have read many of hte postings on here but have only read about side effects.  Can anyone tell me if they have had good results?  At this point each time a new medication is added my mother will try it then refuse to take any more.  She has the sample pack from the doctor but has already said she would not fill the RX.

 


Ttom
Posted: Tuesday, December 6, 2011 7:34 AM
Joined: 11/29/2011
Posts: 182


Diane D wrote:

Just joined forum but have had more experience dealing with Alzheimer patients than I care to think about.  My Grandmother developed Alzheimers many years ago and was enrolled in a research study which is probably what saved me mentally.  Now my mother has been diagnosed and I watch her slowly deteriorate.  It seems that each time she goes to her doctor he gives her something new.  Most recently Axona. 

 

Hello Diane and Welcome. Sorry for what brings you here but happy that you found us. My gosh I guess you do have experience and I wish the best for you.

JAB
Posted: Tuesday, December 6, 2011 11:54 AM
Joined: 11/30/2011
Posts: 740


Hi, Diane, welcome to the new boards.  We've discussed Axona extensively on the old boards.  Quite a few of us -- me included -- have had good results with it.  That's why I'm so excited to see that the company is pursuing drug status.  Current data indicates that the degree to which it helps depends on whether your loved one carries the APOE4 allele.

 

 Do start her off slowly, though, maybe a quarter of a pack for several days, and gradually work your way up.  And give it immediately after a full meal heavy in protein and healthy (unsaturated) fats.  Otherwise, she's likely to have gastrointestinal problems (cramps, diarrhea) until her body adjusts.

 

While this beta site is getting fixed up, come talk with us on the "old" boards, too.

 

http://alzheimers.infopop.cc/eve/forums


Gulf Coast Gal
Posted: Saturday, December 10, 2011 7:23 PM
Joined: 12/4/2011
Posts: 39


How does Axona differ from Cerafolin. My DH was started on Cerafolin back in July, one pill twice a day and I could see a remarkable difference. He has an appointment in January at Mayo to see if he will qualify for a drug trial of some type. Right now I see him undergoing subtle changes as the disease progresses. This seems to be his pattern, he holds steady for awhile and then I notice slight changes which become the new normal for a bit and then the changes again. Over time it just adds up to a general down turn.
Lane Simonian
Posted: Monday, December 12, 2011 11:28 AM
Joined: 12/12/2011
Posts: 4854


Axona is a medical food containing caprylic triglycerides (similar but not exactly the same as coconut oil).  The purpose of Axona is to increase ketone levels in the body.  The primary rationale for this is that ketones can serve as an alternative fuel source for the brain (for a variety of reasons glucose levels decline as Alzheimer's disease progresses).  Ketones also decompose peroxynitrites and this may be their most important function.  In Alzheimer's disease, peroxynitrites oxidize glucose transport systems, choline transport systems, the enzyme choline acetyltransferase, and g proteins coupled to receptors involved in short-term memory (muscarinc acetylcholine), mood (serotonin and opioid), sleep (serotonin and melatonin), social recognition (oxytocin), alertness (dopamine), and smell (oflactory).  They also increase the release of glutamate and the influx of calcium which contributes to the death of neurons.

 

Cerefolin is a prescription medication containing folic acid, vitamin B12, and N-acetylcysteine.  The primary purpose of cerefolin is to lower levels of homocysteine which are high in people with Alzheimer's disease.  In addition to this N-acetylcysteine may increase levels of glutathione which is an important antioxidant.

 

High homocysteine levels lead to high levels of peroxynitrites and glutathione depletion (thus, peroxynitrites exhaust one of the body's few internal means to combat it).

 

The question is whether cerefolin decreases homocysteine levels enough and/or increase glutathione levels enough to alter the progression of the disease in the long-term.  In the case of Axona, the question is whether ketones decompose or scavenge peroxynitrites enough to stop (and perhaps reverse) the progression of the disease.

 

The best scavengers of peroxynitrites (which also reverse part of their oxidative damage) appear to be methoxyphenols (such as eugenol, carvacrol, and thymol) and polyphenols (such as rosmarinic acid, curcumin, resveratrol, and compounds in grape seed extract and true cinnamon extract, for example).  I advocate the use of aromatherapy with essential oils high in methoxyphenols (such as rosemary, sage, thyme, oregano, cinnamon leaf, laurel, and peppermint) because unlike spices or tablets, the compounds in the essential oil directly reach the hippocampus through the system of smell (again the receptors for smell and short-term memory are of the same type, so by partially reversing the loss of smell you also partially reverse the loss of short-term memory).  You can see my posts on the old message boards for more information on this subject.  I have to repeat myself sometimes, just to try to get the critical information down for people looking at a particular post.  The most important point is that in animal studies, clinical trials, and case studies (including my own mother) the use of aromatherapy has produced significant improvements in cognitive function in patients with Alzheimer's disease.


Ttom
Posted: Monday, December 12, 2011 1:08 PM
Joined: 11/29/2011
Posts: 182


 

Until more is known, the Alzheimer's Association doesn't recommend the use of medical foods, including Axona, for the treatment of Alzheimer's disease

 


Gulf Coast Gal
Posted: Monday, December 12, 2011 8:29 PM
Joined: 12/4/2011
Posts: 39


Thanks, that information is very helpful.  As far as aroma therapy goes, I don't think you have anything to lose, only to gain by trying it. I have used it for myself but will now include some for my DH, if nothing else it gives a sense of pleasure.
JAB
Posted: Wednesday, December 14, 2011 10:20 AM
Joined: 11/30/2011
Posts: 740


With all due respect to Lane, the evidence I have found for aromatherapy being beneficial for dementia patients is quite weak, and results have been conflicting and contradictory.  (Note, however, that at least some of the conflicting results may have had to do with experimental design, as opposed to whether aromatherapy per se may be beneficial in some way.)  Some researchers even suggest it's the massage that's helpful, and not the oils at all.

 

However, I may not have found everything there is to find in the research literature. (!!!) I'd be delighted if Lane could post links to reports on clinical trials involving dementia patients that provide solid evidence of the benefits.  (Fair warning, Lane -- I have absolutely no faith in the relevancy of animal models when it comes to dementia.)

 

Also, from what I've read on the subject, there can definitely be adverse effects associated with some aromatherapy products. 

 

Lane, would you please start a thread on aromatherapy, so we can discuss the pros and cons in detail there?


JAB
Posted: Wednesday, December 14, 2011 10:26 AM
Joined: 11/30/2011
Posts: 740


Ttom, that's why I'm so excited Accera is actually going to test caprylic triglyceride as an IND.

 

Ummm... could I please modify your statement?  Until more is known, the Alzheimer's Association doesn't recommend the use of medical foods, including Axona and Cerefolin, for the treatment of Alzheimer's.

 

(At the same time, they don't, as far as I know, recommend against their use.  They're simply withholding judgment.  Many knowledgeable doctors prescribe Cerefolin, and more and more doctors are beginning to prescribe Axona.)


JAB
Posted: Wednesday, December 14, 2011 1:07 PM
Joined: 11/30/2011
Posts: 740


Lane Simonian wrote:

Axona is a medical food containing caprylic triglycerides (similar but not exactly the same as coconut oil).  The purpose of Axona is to increase ketone levels in the body.  The primary rationale for this is that ketones can serve as an alternative fuel source for the brain (for a variety of reasons glucose levels decline as Alzheimer's disease progresses).

 

 

 

That's a simplistic explanation that may be used for marketing purposes for the general public, but it's not at all accurate or complete.  The effects of ketone body therapy are many and diverse.  And ketone body therapy is effective in many diverse neurological disorders.

 

For more information, see, e.g.:

 

Accera/Axona publications:

Henderson ST, Poirier J. Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet. 2011 Oct 12;12:137.
http://www.biomedcentral.com/1471-2350/12/137

Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Costantini LC. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond). 2009 Aug 10;6:31.
http://www.nutritionandmetabolism.com/content/6/1/31

Taha AY, Henderson ST, Burnham WM.  Dietary enrichment with medium chain triglycerides (AC-1203) elevates polyunsaturated fatty acids in the parietal cortex of aged dogs: implications for treating age-related cognitive decline.  Neurochem Res. 2009 Sep;34(9):1619-25.
http://www.ncbi.nlm.nih.gov/pubmed/19301124

Henderson ST. 2008. Ketone bodies as a therapeutic for Alzheimer’s Disease. Neurotherapeutics 5:470-480.
http://www2.prnewswire.com/mnr/axona/36444/docs/36444-Henderson2008Neurotherapeutics.pdf

Costantini LC, Barr LJ, Vogel JL, Henderson ST. 2008. Hypometabolism as a therapeutic target in Alzheimer's disease. BMC Neuroscience 9(Suppl 2):S16.
http://www.biomedcentral.com/1471-2202/9/S2/S16

Studzinski CM, MacKay WA, Beckett TL, Henderson ST, Murphy MP, Sullivan PG, Burnham WM. 2008. Induction of ketosis may improve mitochondrial function and decrease steady-state amyloid-beta precursor protein (APP) levels in the aged dog. Brain Res 1226:209-17.
http://www.ncbi.nlm.nih.gov/pubmed/18582445
(I have a .pdf of the full paper which I'd be happy to send to anyone who is interested.)

Van der Auwera I, Wera S, Van Leuven F, Henderson ST.  2005.  A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr Metab (London) 2:28.
http://www.nutritionandmetabolism.com/content/2/1/28

Henderson ST.  2004.  High carbohydrate diets and Alzheimer’s disease.  Med Hypotheses 62:689-700. 
http://www.ncbi.nlm.nih.gov/pubmed/15082091
(I have a .pdf of the full paper which I'd be happy to send to anyone who is interested. This is a very lengthy and detailed paper, quite interesting.)

Reger MA, Henderson ST, Hale C, Cholerton B, Baker LD, Watson GS, Hyde K, Chapman D, Craft S.  2004.  Effects of b-Hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging 25:311-314.
http://www.numedica.com/literature/Reger%202004.pdf


Related publications:

Pifferi F, Tremblay S, Croteau E, Fortier M, Tremblay-Mercier J, Lecomte R, Cunnane SC. Mild experimental ketosis increases brain uptake of 11C-acetoacetate and 18F-fluorodeoxyglucose: a dual-tracer PET imaging study in rats. Nutr Neurosci. 2011 Mar;14(2):51-8.
http://www.ncbi.nlm.nih.gov/pubmed/21605500

Xiang Y, Shen J. Simultaneous detection of cerebral metabolism of different substrates by in vivo ¹³C isotopomer MRS. J Neurosci Methods. 2011 May 15;198(1):8-15.
http://intramural.nimh.nih.gov/mib/pdfs/Xiang-Shen-2011.pdf

Murray IV, Proza JF, Sohrabji F, Lawler JM. Vascular and metabolic dysfunction in Alzheimer's disease: a review. Exp Biol Med (Maywood). 2011; 236(7): 772-782.
http://ebm.rsmjournals.com/content/236/7/772.full

Swerdlow RH, Burns JM, Khan SM.  The Alzheimer's disease mitochondrial cascade hypothesis.  J Alzheimers Dis. 2010;20 Suppl 2:S265-79. 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883665

Rodolfo C, Ciccosanti F, Giacomo GD, Piacentini M, Fimia GM.  Proteomic analysis of mitochondrial dysfunction in neurodegenerative diseases.  Expert Rev Proteomics. 2010 Aug;7(4):519-42.
http://www.apo-sys.eu/aposys/Publications/Publications2010-pdf/Rodolfo.pdf

Maalouf M, Rho JM, Mattson MP.  The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies.  Brain Res Rev. 2009 Mar;59(2):293-315.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649682

Swerdlow RH. Mitochondrial Medicine and the Neurodegenerative Mitochondriopathies. Pharmaceuticals 2009, 2(3), 150-167.
http://www.mdpi.com/1424-8247/2/3/150/pdf

Prins ML.  Cerebral metabolic adaptation and ketone metabolism after brain injury.  J Cereb Blood Flow Metab. 2008 Jan;28(1):1-16. 
http://multivu.prnewswire.com/mnr/axona/36444/docs/36444-Prins2008KetoneReview.pdf

Barañano KW, Hartman AL.  The ketogenic diet: uses in epilepsy and other neurologic illnesses.  Curr Treat Options Neurol. 2008 Nov;10(6):410-9.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898565/

Gasior M, Rogawski MA, Hartman AL.  Neuroprotective and disease-modifying effects of the ketogenic diet.  Behav Pharmacol. 2006 September; 17(5-6): 431–439.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367001/

Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL.  2000.  D-beta-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proc Natl Acad Sci USA 97:5440 –5444.
http://www.ncbi.nlm.nih.gov/pubmed/16917840

 


judysguy
Posted: Sunday, December 18, 2011 11:04 PM
Joined: 12/17/2011
Posts: 11


Hi JAB,

Continuing the discussion from the old forum:

Despite what the Genetech clinical trails support line told me, Dr. Peskind informs me that she will not be conducting a study of MABT5102A in the VA system for them because they wouldn't accept the VA's rules.  Next study around here is an ADCS trial of reservatrol.  My LO is in the subject registry so if they include people at moderate stage maybe she'll be called.

I'm awaiting a month's supply of MCT Fuel and I figured I'd take your advice to see if my LO responds before pursuing Axona.  I know that it is best to introduce it slowly. The Axona prescribing information suggests 1 TBS for two days, then going up a TBS every other day until the full 5 TBS dose is reached.  Would you recommend the same regimen for MCT oil?

You mentioned elsewhere to give it 5-10 minutes after a full meal with protein and unsaturated fats. The Axona prescribing info says 15-30 minutes.  Have you seen any difference over how long you wait?  Probably the sooner after breakfast the better for my LO, before she gets distracted and into kitchen-cleaning mode.

The graph on APOE4- dose-compliant subjects is certainly compelling.  I hope it helps us as my LO's abilities continue to decrease steadily.

Finally, I'd like to take you up on your willingness to share research papers you've read.  Thanks for posting all of the ones above.  I note that there is one by Henderson and colleagues in ta 2005 Nutr Metab reporting decreased beta amyloid in the mouse model.  I didn't see any references to results in humans, unless it's in the Maalouf paper.  Do you know of any?

A question from your post of March 28, 09:  You state that there are reasons to be concerned that long-term uptake of high doses of the saturated fats may exacerbate the symptoms of AD and speed the progression.  Do you have any references?  You refer in your 4/25/09 post to an analysis of diabetic women in the Nurses Health Study showing this effect, but I couldn't find the publication information  in later posts nor any for the papers that it apparently refers to.

Thanks for the heads-up on Google Scholar and I appreciate your letting me pick your brains.  My internet research time tends to be at night and I try to limit myself to going to bed early enough that I'll have some sleep in case my LO wakes up in the middle of the night wanting to go "home" from our house we've lived in for 25 years.  Consequently it takes me a while to research things.

 

Nothing everybody else here isn't dealing with.


judysguy
Posted: Sunday, December 18, 2011 11:07 PM
Joined: 12/17/2011
Posts: 11


There were supposed to be spaces between the paragraphs in the above post.  Don't know where they went.  

   

Sorry about that.

 

 


JAB
Posted: Monday, December 19, 2011 1:35 PM
Joined: 11/30/2011
Posts: 740


I'm awaiting a month's supply of MCT Fuel and I figured I'd take your advice to see if my LO responds before pursuing Axona.  I know that it is best to introduce it slowly. The Axona prescribing information suggests 1 TBS for two days, then going up a TBS every other day until the full 5 TBS dose is reached.  Would you recommend the same regimen for MCT oil?

Me, I'm a chicken.  I'd do it more slowly than that.  Some loved ones are pretty sensitive to it at first.


You mentioned elsewhere to give it 5-10 minutes after a full meal with protein and unsaturated fats. The Axona prescribing info says 15-30 minutes.  Have you seen any difference over how long you wait?  Probably the sooner after breakfast the better for my LO, before she gets distracted and into kitchen-cleaning mode.

I did?  I usually say "immediately after".  And that's what I do.


Finally, I'd like to take you up on your willingness to share research papers you've read.  

Send me your email addy.  AlzCarer at gmail dot com


I note that there is one by Henderson and colleagues in ta 2005 Nutr Metab reporting decreased beta amyloid in the mouse model.  I didn't see any references to results in humans, unless it's in the Maalouf paper.  Do you know of any?

Are you asking about studies on measuring Abeta in humans who are on ketone body therapy?  Can't think of any off the top of my head.  I know the Accera folks were hoping to collaborate with a group in Canada to do PET analysis, don't know if they ever got that started or not.  Even if they did, the current (experimental) PET dyes bind to plaque, not soluble Abeta, so I don't know how useful the data would be.  (Many researchers think it's the soluble forms that are toxic.)


A question from your post of March 28, 09:  You state that there are reasons to be concerned that long-term uptake of high doses of the saturated fats may exacerbate the symptoms of AD and speed the progression.  Do you have any references?  

Do I have any references?  LOL  I realize you're a newbie, but really!

http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/887106222?r=887106222#887106222

judysguy
Posted: Monday, December 19, 2011 11:51 PM
Joined: 12/17/2011
Posts: 11


JAB wrote:

Me, I'm a chicken.  I'd do it more slowly than that.  Some loved ones are pretty sensitive to it at first.

 
thanks.  Since my LO is taking 4 gm curcumin/day I'm concerned about adding something else whose main side effect can be gastric distress.  I'll start with 1 teaspoon or so.



Finally, I'd like to take you up on your willingness to share research papers you've read.  

Send me your email addy.  AlzCarer at gmail dot com
Done


I note that there is one by Henderson and colleagues in ta 2005 Nutr Metab reporting decreased beta amyloid in the mouse model.  I didn't see any references to results in humans, unless it's in the Maalouf paper.  Do you know of any?

Are you asking about studies on measuring Abeta in humans who are on ketone body therapy?  Can't think of any off the top of my head.  I know the Accera folks were hoping to collaborate with a group in Canada to do PET analysis, don't know if they ever got that started or not.  Even if they did, the current (experimental) PET dyes bind to plaque, not soluble Abeta, so I don't know how useful the data would be.  (Many researchers think it's the soluble forms that are toxic.)
Right, the oligomeric forms.  The keynote speaker at the Regional Alz Assoc conference this spring (the honcho from the Mayo clinic whose name eludes me) showed slides demonstrating that the AB levels are pretty much established by the time symptoms appear and after that the tau starts climbing with neuron death.  Since my LO is moderate stage I'm thinking dealing with tau might be more productive.  Of course, you're aware of all this


A question from your post of March 28, 09:  You state that there are reasons to be concerned that long-term uptake of high doses of the saturated fats may exacerbate the symptoms of AD and speed the progression.  Do you have any references?  

Do I have any references?  LOL  I realize you're a newbie, but really!

http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/887106222?r=887106222#887106222 
Uh......maybe I should have phrased that question differently?  Seriously, I had missed that thread and I greatly appreciate the link.  Speaking of saturated fats, the proponents of saturated fat not affecting heart disease or AD point to a metanalysis published in June last year.  A friend just gave me a copy of Consumer Reports health newsletter which quoted critics of that paper as saying the methodology was flawed and there was a potential conflict of interest with one of the authors.
I'm not really interested in spending the rest of my life concerned with finding out who's right in that particular argument.  I'm interested in trying to help my LO so sticking with Axona or its closest mimic seems safest and then moving on to look at other possible options.
Thanks again for all of the useful information.  Once I've digested it I will probably start bugging you about hueperzine which I didn't look into since I assumed it was similar to donepezil or the other AchE inhibitors.
 


JAB
Posted: Wednesday, December 21, 2011 4:11 PM
Joined: 11/30/2011
Posts: 740


Huperzine A is indeed similar to Aricept/donepezil, Razadyne/galantamine, and Exelon.  See:
http://www.alzcompend.info/?p=244
JAB
Posted: Wednesday, December 21, 2011 4:18 PM
Joined: 11/30/2011
Posts: 740


"A friend just gave me a copy of Consumer Reports health newsletter which quoted critics of that paper as saying the methodology was flawed and there was a potential conflict of interest with one of the authors."

 

 Oh, hey, could you send me a copy?  Or give me the reference to the paper?  I saw the abstract of the meta-analysis but couldn't get my hands on the full paper.  I know it was promptly blasted by one of the leading authorities in the field, but I couldn't get my hands on his letter to the editors, either.


judysguy
Posted: Friday, January 6, 2012 10:42 PM
Joined: 12/17/2011
Posts: 11


JAB wrote:

"A friend just gave me a copy of Consumer Reports health newsletter which quoted critics of that paper as saying the methodology was flawed and there was a potential conflict of interest with one of the authors." 

  

 Oh, hey, could you send me a copy?  Or give me the reference to the paper?  I saw the abstract of the meta-analysis but couldn't get my hands on the full paper.  I know it was promptly blasted by one of the leading authorities in the field, but I couldn't get my hands on his letter to the editors, either.
 


Here's the meta-analysis from Siri-Tarino et al.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824152/

Here's the comment by Stammler:

http://www.ajcn.org/content/91/3/497.long#content-block

There are also a couple of comments by others but I could only find the original authors responses, including one in which they state that Krauss's association with the American Dairy Council ended years before this study.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904040/   Still, he does list the the American Cattleman's Beef Association and the Atkins foundation as being the sources of his research support, so I do have to wonder about possible bias.

The American Journal of Clinical Nutrition seems to make all of its content available for free, bless them.

On a different question, my LO is up to 3 TBs of MCT fuel per day with no problems so far.  Do you have a recommended amount?  It depends on how effective the capric triglyceride is in making ketone bodies, I guess.  It would take 8-2/3 TBs of MCT fuel to get to the 20 gm of caprylic triglyceride in Axona but only 2-1/2 if the capric triglyceride were as effective.

 

Thanks for sending the two papers, I haven't had a chance to look at the other references yet (which might tell me how muc capric triglyceride is used).  The beagle paper seemed to show a decrease in APP as well as amyloid itself, which would mean less amyloid production  down the road, I think. You've mentioned your concerns about animal studies, especially in the transgenic mice.  How about the beagles, where the ketones seem to affect a normal process of aging; or knock-out mice; or treatment of wild mice that show changes?  Just curious.

Next week my LO and I are going on our first plane trip since she was diagnosed.  
Wish us luck.


JAB
Posted: Saturday, January 7, 2012 11:31 AM
Joined: 11/30/2011
Posts: 740


Thanks Guy!  (My, but that's a lively little exchange, isn't it.)

 

Capric is going to be fairly close to caprylic in terms of its ketogenicity, so I'd hazard a guess in the neighborhood of 5 Tablespoons Fuel.  That's what I gave my husband before Axona came on the market.

 

Animal models need to be taken with a very large grain of salt.  That said, I'd look more favorably on studies with beagles than any type of mice.  Dogs can develop canine dementia.

 

Mice do not develop dementia.  And their genetic makeup differs so much from humans' that only a very small part of the known AD cascade can be inserted into their genome.  Many different strains have had to be developed just to (hypothetically) look at some parts of the cascade.


ClaireB
Posted: Wednesday, March 7, 2012 8:11 PM
Joined: 3/7/2012
Posts: 1



rose_ro
Posted: Thursday, March 8, 2012 10:34 AM
Joined: 12/21/2011
Posts: 2431


JAB wrote:

OK, folks, just to inaugurate this forum ... Accera has announced that the FDA has accepted its application for a long-term (6 months double-blind placebo-controlled plus 6-month open label) Phase II/III clinical trial for "AC-1204" as an IND.

 

http://clinicaltrials.gov/ct2/show/NCT01211782

 

Axona, which is based on caprylic triglyceride, is sold as a prescription-only "medical food".  The testing that is required for a product to be sold as a "medical food" is quite limited in comparison with the testing that is needed for an IND (investigational new drug).  The data that has been developed to date appears very promising -- and many of us have reported that Axona is beneficial to our loved ones.

 

Because of the limited testing, many doctors are leery of recommending Axona.

 

Well, the active ingredient in AC-1204 is caprylic triglyceride.  I.e., we're going to have a chance to see just what Axona-by-another-name (possibly in a different formulation, couldn't find info on that) can really do!

 

Earlier studies indicated there may be a significant difference in the degree to which Axona can help patients with vs without the APOE4 allele.  This clinical trial (which is not yet open for recruitment, but which will be conducted in St Petersburg FL) will be limited exclusively to APOE4(-) Alzheimer's patients.


  I have a very serious issue with their use of a synthetic sweetener, which I believe is bad for the brain.  Why use it?
Lane Simonian
Posted: Thursday, March 8, 2012 10:56 AM
Joined: 12/12/2011
Posts: 4854


The argument for Axona (and other products that contain ketone bodies such as coconut oil and MCT oil) is that they provide an alternative energy source to the brain and they act as antioxidants (which is critical since both oxidative damage and problems in glucose transport are two hallmarks of Alzheimer's disease).

 

http://www.ncbi.nlm.nih.gov/pubmed/19664276 

http://www.ncbi.nlm.nih.gov/pubmed/16940764 

 

These products are not without side effects including nausea, cramping, and diarrhea. However, they may provide some benefit in the treatment of Alzheimer's disease. 


Myriam
Posted: Thursday, March 8, 2012 12:34 PM
Joined: 12/6/2011
Posts: 3326


I can only speak for what Axona does for me. I was traveling for two weeks and forgot to reorder Axona. I went for 5 days without it and noticed a distinct decline in my cognition. The 5th day was the worst with me having moved from a strong stage 2, to clearly falling into in stage 3. I am on my 3rd day weaning myself back on Axona and am almost all the way back to stage 2. BTW, I have the presinilin 1 gene, not APOE.
Lane Simonian
Posted: Thursday, March 8, 2012 1:34 PM
Joined: 12/12/2011
Posts: 4854


Myriam reminded me of a point that I should have made.  Axona seems to have less of an effect on Alzheimer's patients who have the APOE4 gene at least in the early stages of the disease. 

 

http://www.tangledneuron.info/the_tangled_neuron/2010/03/update-on-axona.html 

 

This may be because Axona in conjunction with the APOE 4 gene further impedes a pathway that provides some protection against Alzheimer's disease.  In people with presenilin gene 1 mutations this pathway is already cut off altogether so the Axona won't make a negative difference.  Axona should work for anyone with Alzheimer's disease as the disease progresses because it is an antioxidant (as long as it can scavenge peroxynitrites, which I haven't been able to determine for certain yet).

 

http://www.ncbi.nlm.nih.gov/pubmed/16960657 

http://circres.ahajournals.org/content/99/8/829.full 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC449766/ 

 

All I do is listen to positive stories, and then try to figure out the biochemistry behind those positive stories (developing the hypothesis took me three years, much of it spent in utter confusion, but now its easy most of the time).  If someone says something works for them, I am almost always able to find out now the reason why it worked (that's not to say I find the right explanation every time).   

 

 


judysguy
Posted: Tuesday, March 13, 2012 12:51 PM
Joined: 12/17/2011
Posts: 11


My LO has now been taking 5 Tbs of MCT Fuel for 2 months and has continued to decline.  Her clock drawing at 45 days wasn't any better than before she started and her ADL functioning is still going downhill.

 

I've got enough MCT Fuel for three more weeks but she's decided she doesn't like the taste even though I mix it with OJ.  Does anybody see any reason to continue having her take it?

 

Thanks JAB for suggesting I try the MCT oil before driving 4 hours round trip to the doc that does prescribe Axona and paying for the visit and prescription out of pocket.  It looks like she may have APOE4 although we don't know her genotype.  That means neither souvenaid nor bapineuzamab would work either.

We haven't had any luck with 9 months of 2 gm bid of Longvida curcumin either.  I note the recent finding that vitamin D3  is needed to activate one of the classes of macrophages in conjunction with the curcumin.  My LO takes a fair amount of D3 with her calcium supplements and her blood levels of D are good.  I have 3 more months supply of Longvida so after it is gone I guess it is time to stop looking for the magic bullet.


Lane Simonian
Posted: Tuesday, March 13, 2012 9:22 PM
Joined: 12/12/2011
Posts: 4854


In addition to questions regarding the efficacy of coconut oil, MCT oil, or Axona for people with the APOE4 gene, questions also exist for whether they help people at any stage of Alzheimer's disease or whether they limit the progression early on and not later.  I don't think an answer exists to this question yet. 

  

There are no magic bullets in the treatment of this disease, but there are possibly semi-magical bullets.  The key to treating this disease is to not only limit the formation of peroxynitrites, but to scavenge them and to reverse the oxidative and nitration damage that they do to critical enzymes, proteins, and receptors. Certain scavengers are not very bioavailabe to the brain and efforts to make them so have not met with much success so far (Longvida curcumin, for instance).  Curcumin contains methoxyphenols.  So do various essential oils that can be inhaled into the brain via aromatherapy (cinnamon leaf, clove, oregano, mountain savory, rosemary, thyme, lemon balm, peppermint, bay laurel, orange, grapefruit, lemon, etc.).  Methoxyphenols may not be the best peroxynitrite scavengers, but they are one of the few that can be delivered in concentrated doses to the brain intranasally.   

If you try aromatherapy, give it some time.  It generally takes three weeks to a month to see much difference.  Twice a day for a few seconds under each nostril with four or five essential oils at a time should be safe.  The use of aromatherapy results in better sleep, recognition, alertness, awareness, and some improvements in some aspects of short-term memory (recognition of place and time, to a certain extent, for instance).    


Lane Simonian
Posted: Tuesday, March 13, 2012 9:45 PM
Joined: 12/12/2011
Posts: 4854


A couple of more points about treatments for Alzheimer's disease.  Acetylcholinesterase inhibitors (Donepezil/Aricept, Rivastigmine/Exelon, Galantamine, and Huperzine A) do not stop the progression of Alzheimer's disease.  Acetylcholinesterases are only good for symptomatic treatment of the disease early because they just inhibit acetylcholinesterase activity rather than inhibiting the enzyme (phospholipase C) that causes high levels of acetylcholinesterases in the first place.  By the late stages of the disease, acetylcholinesterase activity has declined by 85 percent, and acetylcholinesterases work then (to the extent that they work as all) as antioxidants. 

 

For moderate to the late stages of the disease, memantine/Namenda acts as a partially block for the NMDA receptor, inhibiting the influx of calcium and the efflux of glutamate both of which are toxic to neurons and other brain cells.  Magnesium is the natural gate for this receptor, but its intracellular levels are lowered by peroxynitrites.  Magnesium threonate is being studied as a way to increase magnesium in the brain to protect neurons.  Peroxynitrite scavengers will also increase magnesium levels in the brain inhibiting the death of neurons and surrounding cells.