While We Wait for a Scientific Miracle Cure – Investigating Ways to Prevent Alzheimer’s Disease

While We Wait for a Scientific Miracle Cure:
Investigating Ways to Prevent Alzheimer’s Disease

By Guest Blogger,
Tyler Kokjohn

Amyloid plaques

photo courtesy of Alex Roher

If you follow Alzheimer’s disease (AD) research news you may have noticed momentous discoveries that might lead to a cure are announced regularly.  A Google search of “Alzheimer’s disease breakthrough” will provide numerous examples.  Regrettably, these promising results have not been translated into effective treatments and AD continues to take a terrible toll.

The good news is that average life expectancy has increased substantially over the last hundred years since Alois Alzheimer described the first case of early-onset dementia that has come to bear his name.  The bad news is that a significant risk factor for AD development is advanced age and we have experienced an ominous increase in dementia incidence as people live longer.  The really bad news is that this trend is projected to get even worse in the future (1).  The financial and other burdens imposed by AD might become unimaginably difficult if these predictions are accurate.

Aware potential disaster looms ahead, scientists are working to understand the mechanisms behind AD pathology and develop ways to halt it.  Decades of effort have revealed how the cardinal brain lesions of AD dementia such as amyloid plaques and neurofibrillary tangles are constructed.  Researchers have exploited an understanding of the key molecules involved and how they are produced to devise ways to disrupt amyloid plaque deposits or prevent their formation in the first place.  Unfortunately, clinical trials of these strategies have yielded consistently disappointing results prompting introspective searches for new treatment application modes (2) and targets.

While we await the outcomes of important new clinical trials and hope for the best, it is clear that an effective and practical AD cure has been elusive.  In addition, dementia pathology pathways and processes have turned out to be far more diverse than initially assumed, suggesting aspirations for a single, simple cure might be an impossible dream.  Both the general public and scientific community are anxious for progress.

Tangles

photo courtesy of Alex Roher.

A recent post on Alzforum highlighted some tantalizing findings suggesting that dementia rates are dropping in some regions (3).  Several factors are in play, but AD development has long been appreciated to exhibit a sensitivity to environmental factors.  One possibility is that taking steps to improve the overall health of the public such as identifying persons with cardiovascular issues like high blood pressure and treating them early might reap the additional reward of lowering the incidence of dementia.  These findings provide a potent rationale and impetus to expand efforts to identify the most significant environmental/lifestyle impacts on AD risk.  Recognizing the factors exerting the greatest effects on lifetime brain health may suggest simple, eminently practical interventions to decrease the dementia threat in the near term.  Unfortunately, these efforts may not seem as glamorous or deemed as news-worthy as the more traditional research strategies which have been heavily promoted and financed to date.

Intense efforts to comprehend and control AD have been proceeding for over 30 years.  However, at best any traditional pharmacological cure for AD may lie somewhere in a murky future.  That means the virtually unheralded and currently underfunded work to clarify critical environmental risk factors might actually spare many from developing dementia in the potentially long interim before an AD cure is ready to go as well as minimize the need for such probably expensive interventions if and when they become available.  While we wait patiently for a scientific miracle, it is important to foster and promote all approaches that might contribute significantly to the goal of preventing AD.

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(1)    http://www.alz.org/facts/

(2)    J. L. Molinuevo et al. 2016. Ethical challenges in preclinical Alzheimer’s disease observational studies and trials: Results of the Barcelona summit. Alzheimer’s & Dementia (Epub ahead of print) http://www.alzheimersanddementia.com/article/S1552-5260(16)00076-5/fulltext

(3)    M. B. Rogers. 2016. Dementia incidence in Britain, dropped, mostly in men. Alzforum, 21 April 2016  http://www.alzforum.org/news/research-news/dementia-incidence-britain-dropped-mostly-men

 

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Titanic Opportunities

Titanic Opportunities
By Guest Blogger,
Tyler Kokjohn

Titanic

The emergence of Zika virus in the Americas has prompted swift actions by public health authorities to forestall a growing regional epidemic of potentially serious infections (1).  Because no vaccines or specific anti-viral treatments for Zika virus infections are available, proactive protection efforts focus on breaking the chain of transmission of this mosquito-borne virus to humans.  That involves getting rid of standing water and removing trash to eliminate mosquito breeding sites, careful use of repellents and insecticides and keeping window screens in good repair.  These simple actions are proven mosquito-borne disease prevention measures.

The Zika virus threat has produced an interesting opportunity for opinion leaders seeking to advance the acceptance and use of some new mosquito control methods (2).  Field tests have confirmed that mass releases of genetically modified mosquitoes can dramatically suppress disease vector populations and the use of GMO mosquitoes to control transmission of viruses like Zika and Dengue in Key West, Florida, is now being evaluated.  Proponents suggest this new technology is tested, scalable and ready to roll, if only regulators would simply expedite approval.  The mosquito makers are anxious to go, but the problem is that this specific method has not yet been proven to suppress the transmission of any human disease. Whether this approach will actually stop Zika infections under the conditions present in Key West is not an established fact, it is a hypothesis that must be tested.  Although the field trials were enormously encouraging, at this moment it is premature to imply GMO mosquitoes are a sure means to halt Zika virus transmission or that this technology represents our best hope to control the menace now facing us.  Some groups may find it frustratingly slow, but there is no urgent need to short circuit the efficacy study processes.

The new, transformative genetic engineering technologies offer alluring prospects for a better future.  However, we cannot be certain concepts like controlling diseases with GMO mosquitoes that look absolutely unbeatable on the drawing board will actually work as advertised and intended until they are tested.  In addition, it is important to determine through objective assessments whether new technologies have any adverse environmental impacts.  Releasing GMO mosquitoes may have a theoretically low level of risk, but more aggressive environmental manipulation approaches such as gene drives may be difficult or impossible to reverse if they produce adverse events.  However, until these promising new strategies are evaluated fully, estimates of their true benefits and risks are little more than opinions.

Fully assessing environmental risks of proposed actions may be challenging because some adverse events unfold over long periods in unanticipated ways.  Paralytic poliomyelitis (‘polio’) was once an extremely rare disease of infants.  However, mass epidemics of polio paralysis began to appear in the twentieth century as communities improved their water supplies.  Cleaning up municipal water sources decreased deaths due to typhoid fever and cholera, but unexpectedly replaced those scourges with something new.  When water supplies were typically contaminated with sewage, babies were infected with polioviruses during the lifespan period when they were least likely to be paralyzed.  Cleaning up the water meant that poliovirus infections came later in life when paralysis was a far more likely outcome.  A simple and obviously beneficial change in living conditions had literally set the stage for the great polio epidemics to come.  This unanticipated adverse event took years to become apparent and was impossible to predict before the fact of its emergence.  Poliomyelitis epidemics were finally controlled through the implementation of mass vaccination programs (3).

Sometimes even simple changes without any obvious human health implications turn out to become enormously significant and threatening.  Salvaging slaughterhouse waste products and feeding them back to cattle led to a massive epidemic of bovine spongiform encephalopathy (BSE), sometimes called mad cow disease, in Great Britain.  This re-feeding practice is believed to have unwittingly amplified pathologic prions (infectious proteins) to the point at which cattle started to exhibit obvious signs of neurologic disease.  Almost simultaneously in the same geographic region a new prion disease, new variant Creutzfeldt-Jakob disease (vCJD), appeared in humans. These striking correlations suggest the pathologic prions causing the mad cow epidemic had somehow invaded human populations.  The ultimate consequences of these events on human health remain uncertain.

Clearly, every adverse consequence of change cannot be readily predicted or easily mitigated.  Genetic engineering technologies are novel and still in the trial-and-error phases.  Not even all the laboratory experiments have turned out as expected (4).  As new environmentally aggressive concepts like gene drives are touted as solutions to challenging problems it is important to bear in mind that our world can be unpredictable and inhospitable to human manipulations (5).  Hard experience confirms that comprehensive efficacy testing coupled with long-term surveillance to reveal any consequential negative changes must remain part of the decision making processes necessary for regulatory agency approvals.

The promise of genetic engineering technology is immense.  Whether or not it ultimately proves to be titanic depends on how wisely we manage it.

References:

1.) http://www.nytimes.com/reuters/2016/04/13/world/europe/13reuters-health-zika-microcephaly.html
2.) http://www.nytimes.com/2016/04/06/opinion/mosquito-vs-mosquito-in-the-battle-over-the-zika-virus.html
3.) http://www.uh.edu/engines/epi1527.htm
4.) http://www.nature.com/news/hiv-overcomes-crispr-gene-editing-attack-1.19712
5.) http://www.nytimes.com/2016/04/17/opinion/sunday/tweaking-genes-to-save-species.html

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Stop Telling Me I Need To Read The Seth Material. I Have. I Don’t. It’s Crap.

jane_robnotes2I will never figure out why so many folks are so taken in by the allegedly channeled words Jane Roberts spoke as the character “Seth.” The basic tenet of Seth’s philosophy is demonstrably untrue. You can hear Jane/Seth speak it on the front page of http://www.sethlearningcenter.org – but I’ll sum it up for you here: your beliefs create reality.

From the aforementioned speech:

“…. [I]f you believe that you are poor, and always will be, then so your experience will so prove to you. Your beliefs meet you in the face when you look in the mirror. They form your image. You cannot escape your beliefs. They are, however, the method by which you create your experience.”

Beliefs and self-image are powerful factors in one’s life to be sure. But the end-all-be-all? Hardly. I have believed my entire adult life that I would likely die broke and alone–and not in the depressing way that that sounds. Well wait, let’s back up… Years ago, I had a “spiritual” unfolding for which I had no belief, not even an image of what that could be like, let alone that it would happen to me. And a lot of what happened was the blossoming of things I did not believe in. Had they not happened to me I would still, to this day, brush them off as silly New Age notions. As a result of these spiritual shenanigans, I became absolutely contented to live alone, die alone, and in poverty. In fact, I’m still contented to do that but as fate would have it, I’ve fallen in love, we’re talking about marriage, and certainly moving in together in our dream home very soon.

I did not believe it. I did not want it. I do not need it in the dysfunctional “you complete me” way. But I gracefully accept my good fortune here and realize that perhaps the greatest illusion we have in life is our sense of control, of mastery over anything, because the one thing that is true that is missing from the Seth material is that life throws ya curve balls whether you believe you’re in the game or not. And sometimes the ball hits you as you stand at home plate. bat in hand, daydreaming about creating a sandwich. Yes, sometimes the pitch hits you and you get a free walk to first sending the player on third home and your team wins.

Sometimes poor people who believe they’ll always be poor win the lottery. Sometimes you don’t know you’re playing the lottery–like when Oprah has a car waiting for you when you thought you were just going to see her interview someone. And sometimes you’re poor, believe you deserve to be rich, and still die broke. Like most poor people.

Sometimes you think you’re on top of the world and you crash. You get sick. You die young. You don’t die young enough. You blah-blah-blah. You get it. Because you live here. Seth doesn’t live here. So Seth doesn’t get it.

That’s the best I can say for “him.”