Quest for Alzheimer’s Vaccine Hitting Roadblocks

Quest for Alzheimer’s Vaccine Hitting Roadblocks

Story Highlights

  • Developing a vaccine for Alzheimer’s disease (AD) has been an elusive quest for pharmaceutical research companies for more than 20 years, generally focusing on preventing accumulation of amyloid plaques and tau tangles, two of the most prevalent hallmarks of the disease.
  • A highly anticipated experimental Alzheimer’s vaccine was pulled from pre-clinical testing when it was shown to cause dangerous brain inflammation in a small number of patients.
  • Several vaccines are in the pipeline now, but it is still uncertain whether reduction of the plaques and tangles will translate into any cognitive benefits for AD patients, or whether other treatments may be more useful in the long run.

Historically, efforts to produce a vaccine to prevent Alzheimer’s disease (AD) have focused primarily on reducing the earliest hallmarks of the disease, both products of an overproduction of normal self-proteins. First to show up are “amyloid plaques,” that accumulate as insoluble clusters between nerve cells. A little later in the disease progression, neurofibrillary tangles form twisted, insoluble fibers inside the nerve cells. Together, the plaques and tangles contribute to the degeneration of the neurons (nerve cells) in the brain characteristic of AD.1

Twenty years ago, Johnson & Johnson’s AN1792 Alzheimer’s vaccine showed early promise in terms of safety and tolerability, but was pulled from phase 2 testing when six percent of patient volunteers developed an immune-mediated brain inflammation (meningoencephalitis), and one person died. Since then, several other vaccines have gone into development, all attempting to reduce accumulation of the damaged target proteins without provoking the dangerous brain inflammation. Those using DNA or peptides against AD have generally not provided a robust immune response,2 and experimental approaches targeting the tau tangles in mice have raised concerns about the potential for neuroinflammation.

The actual role of inflammation, both in AD and in vaccination in general, may complicate the course of vaccine development. As described in an earlier article in The Vaccine Reaction, “There is general agreement that the vulnerable AD brain exhibits both signs of inflammation and stimuli for inflammation, in the form of the classic plaques and tangles characteristic of the disease, yet whether the inflammation is causing, promoting or worsening the damage… or working to remove the accumulated damage resulting from a different disease process remains somewhat in question.”3

New Vaccines in the Pipeline

Unlike “passive” vaccination—creating vaccines using pre-formed antibodies against amyloid or tau proteins for injection into people with active AD—other researchers are taking an “active immunotherapy” approach, aiming to inject the antigen itself and  trigger the body to mount its own antibody response, with the ultimate hope of targeting the damaged proteins before the onset of symptoms of AD.4

Roger Rosenberg, MD, founding director of the Alzheimer’s Disease Center at University of Texas Southwestern in Dallas, TX believes the active approach represents a better chance to vaccinate against AD. Injecting DNA coding for amyloid into the skin rather than the muscle, his team reports that the immune response generated in their laboratory mice showed successful inhibition of the buildup of amyloid plaques by 40 percent, also preventing the subsequent buildup of tau tangles by 50 percent. Although no adverse reactions were reported,5 this vaccine is years away off from being available for use in human patients as it is still in animal trials.

Also hoping to create a vaccine that will work before symptoms appear is United Neuroscience, a small family biotech firm developing UB-311, a synthetic peptide vaccine. United Neuroscience has recently completed a small phase 2a trial of that experimental Alzheimer’s vaccine in 42 human patients.6 Anti-amyloid antibodies were reportedly produced in 96 percent of patients, without serious side effects at either of the two doses studied. Although the company observed some trends suggesting improvements in secondary measures, such as amyloid deposits in the brain and assessment scales for AD, larger and longer-term studies are needed before conclusions can be drawn.7

One of the drawbacks common to all AD vaccines that target the amyloid buildup is the controversy surrounding the amyloid hypothesis itself. According to Chairman of Stanford’s Neurology Department and co-founder of Pharmatrophix, Inc., a private pharma and biotech firm, “Any therapy centered on going after amyloids is dependent on how accurate the amyloid hypothesis is, and that hypothesis continues to be questioned.”8 Even in the early “successful” vaccine that was stopped because of the unforeseen brain inflammation, the “progression of the AD dementia and cognitive decline was unchanged and did not correlate to the reduction in brain ameloid.”9

Other vaccines under development that target the accumulation of beta amyloids include Novartis’ CAD106 (currently in phase II/III testing), Araclon Biotech’s ABvac40 (phase II), AC Immune’s ACI-24 (phase I/II), and Lundbeck/Otsuka’s Lu AF20513 (phase I). Two others are addressing the possibility that the later development of the tau tangles might be more effective: Axon Neurosciences’ AADvac-1 (phase 2) and J&J/AC Immune’s ACI-35 (phase 21).10

Nine Vaccine Studies Also Show Progress in AD

In other arenas, the search also goes on to treat and prevent Alzheimer’s disease. A small trial of a multi-faceted treatment approach reported significant reversal of AD symptoms in nine of ten subjects, with all responding subjects able to return to pre-AD activities such as jobs they’d had to leave, with benefits sustained for up to two and a half years. The only non-responder was a patient diagnosed with late stage AD.

Noting that no single drug has been able to effectively reverse, or even slow, the progress of AD, Dale Bredesen, MD of UCLA and Buck Institute, used a broader-based, personalized approach for this study. Explaining that even a small impact on several different disease aspects may have a profound effect overall, he likened AD treatment to fixing a roof with 36 holes in it. “The drug may have worked, and a single hole may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much.”11

Also reinforcing the concept of complex biological factors culminating in AD and other brain dysfunctions, nutritional support may play an important role, particularly for brain inflammation. Studies have shown that curcumin, the active ingredient in turmeric, may have a profound effect on brain health. A small, double-blind, placebo-controlled study out of UCLA followed 40 adults between the ages of 50 and 90 with mild memory problems. Study subjects were randomly assigned to receive either a placebo or 90 milligrams of curcumin twice daily for 18 months.

Gary Small, MD, lead author of the study, showed that, “The people who took curcumin experienced significant improvements in their memory and attention abilities, while the subjects who received placebo did not … In memory tests, the people taking curcumin improved by 28 percent over the 18 months. Those taking curcumin also had mild improvements in mood, and their brain PET scans showed significantly less amyloid and tau signals in the amygdala and hypothalamus than those who took placebos.”12 13


References:

1 Amyloid Plaques and Neurofibrillary Tangles. Bright Focus Foundation Dec. 21, 2017.
2 Alves RPS. Alzheimer’s Disease: Is a Vaccine Possible? Braz J Med Biol Res June 2014.
3 Raines K. Chronic Inflammation in Alzheimer’s Disease. The Vaccine Reaction Nov. 30, 2017.
4
Newman T. Alzheimer’s Vaccine Draws Closer. Medical News Today Nov. 21, 2018.
5
Ibid.
6
Vance A. A First Step for a Family Biotech’s Vaccine Against Alzheimer’s. Bloomberg Businessweek Jan. 16, 2019.
7 Taylor P. United Neuroscience Inches Closer to Alzheimer’s Vaccine Prize. Pharmacophorum Jan. 28, 2019.
8 See Footnote 6.
9
Lambracht-Washington D. Advances in the Development of Vaccines for Alzheimer’s Disease. Discov Med May, 2013.
10 See Footnote 7.
11
Wheeler M. Memory Loss Associated With Alzheimer’s Reversed for First Time. UCLA Newsroom Oct. 2, 2014.
12 Mercola J. Curcumin Helps Patient Recovery. Mercola.com Jan. 28, 2019.
13 Hopper L. Curcumin Improves Memory and Mood, New UCLA Study Says. UCLA Newsroom Jan. 22, 2018

9 Responses to "Quest for Alzheimer’s Vaccine Hitting Roadblocks"

  1. Linda Adsit   February 7, 2019 at 1:45 pm

    “A small trial of a multi-faceted treatment approach reported significant reversal of AD symptoms in none [?] of ten subjects, with all [?] responding subjects able to return to pre-AD activities such as jobs they’d had to leave, …”

    This sentence states a positive and a negative trial result, both that subjects experienced reversal of symptoms and that none of them was able to return to pre-AD activities.
    One of these must be wrong. Either the subjects did, or did not, have positive outcomes. Can you please explain these statements from the article?

    Reply
  2. Marco Caceres   February 7, 2019 at 2:09 pm

    Thank you Linda. I’ve made the correction.

    Reply
  3. Britt Lind   February 7, 2019 at 3:21 pm

    In 1971, it was found that deceased Alzheimer’s patients had two to three times more aluminum on their brains than normal brains. Research through the decades have confirmed that aluminum on the brain is the cause of most Alzheimer’s. But the aluminum industry did not like when, in the early 1980s, health professionals told the public to get rid of their aluminum products to avoid getting Alzheimer’s, so Big Pharma went back to what they had been doing for 100 years — looking for an “animal model” to Alzheimer’s which, of course, does not exist. Drugs and vaccines are not the answer to Alzheimer’s or most diseases, prevention and detoxification is.

    Reply
  4. Mary   February 7, 2019 at 5:34 pm

    Thank heaven they are having problems getting a good vaccine for Alzheimer’s. That has probably slowed down the decline of health in those patients.

    Focus on lifestyle choices instead and avoid GMO’s, glyphosate-laden foods as much as you can.

    Do not count on the CDC, AMA or HHS to go that route.

    Reply
  5. Joy   February 7, 2019 at 8:09 pm

    The latest research has shown that the amyloid plaque is the result of inflammation, a protective response, not the cause of Alzeimer’s and dementia. Dr. Dale Bredison has had exceptional results REVERSING Alzeimer’s with lifestyle changes which stop the inflammation and heal the brain. As usual, Pharma is looking for a pharmaceutical answer to a lifestyle (including stress and diet) problem.

    Reply
  6. Ed Nichol   February 9, 2019 at 2:27 am

    Your thoughts should be directed towards improving cell function. Decide on how the body normally removes trash material from non vascular areas and you will then understand the value of improving cell, nerve cell function. Therefore, mitochondrial repair and function ( Ubiquinol 500mg minimum/day ) , nutrient demand/delivery ( forced activity in the form of talking, moving, music, memories etc, ) , mineral management, ( numerous chelation programs ) , protein management ( regular short protein fasts with basic fat diet ) , and DHA

    Reply
  7. Christine K   February 11, 2019 at 4:27 am

    A vaccine for Alzheimer’s. How ironic.

    The rate of Alzheimer’s will start to go down in about two decades when the older autistics age into the late-onset Alzheimer’s age demographic.

    Supposedly autism confers a certain amount of protection against Alzheimer’s. Maybe because one can’t “get” what one has already “got”?

    Reply
  8. Valerie Griner   April 10, 2019 at 2:31 pm

    I feel certain that the ALUMINUM in vaccines will be just what these poor patients need! It is most likely the genetic engineering in vaccines that started this inflammatory “cascade” in these Alzheimer’s patients…the blocking of enzymatic pathways and other processes(such as “molecular mimicry”). I also believe that scientists already KNOW what causes most diseases and “SYNdromes,”(like cancer, for example). I recently read an article entitled…”There is No Profit In Curing Disease.” This just about sums it up.

    Reply
  9. johnny   June 25, 2019 at 1:02 pm

    There is no current treatment for dementia/alzheimers so what in the world would be the financial motive for not creating a cure?

    Each of these vaccines mentioned in the article is different from the next, you can’t just lump all “vaccines” together like they’re all the same, and nowhere is it mentioned that any of these contain aluminum.

    Alzheimers patients have more aluminum in the brain because it sticks to tangled tau proteins and amyloid plaque instead of just flowing through and getting filtered out by the liver like normal.

    There is no connection between GMO’s and alzheimers. glyphosate is linked to cancer, not alzheimers.

    A healthy lifestyle can delay alzheimers but doesn’t necessarily prevent it.

    “genetic engineering in vaccines” just lmao. you’re using words and you don’t even know what they mean.

    and vaccines don’t cause autism you dense folks.

    Reply

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