By now it’s not news that scientists at Case Western have successfully used a cancer drug to clear plaques from the brains of mice that were engineered to have Alzheimer’s, resulting in a reversal of rodent dementia. The hope is that this drug will do the same for humans.

Here is a more in-depth explanation of Bexarotene (“Drug Reverses Alzheimer’s Symptoms in Mice”):

Alzheimer’s disease arises in large part from the body’s inability to clear naturally-occurring amyloid beta from the brain.
In 2008, Case Western Reserve University researcher Gary Landreth, professor of neurosciences at School of Medicine, discovered that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins. […] The elevation of brain ApoE levels, in turn, speeds the clearance of amyloid beta from the brain. Bexarotene acts by stimulating retinoid X receptors, which control how much ApoE is produced. …bexarotene improved memory deficits and behaviour even as it also acted to reverse the pathology of Alzheimer’s disease [and] worked quickly to stimulate the removal of amyloid plaques from the brain.
[T]he drug addresses the amount of both soluble and deposited forms of amyloid beta within the brain and reverses the pathological features of the disease in mice.

Here is my visual explanation gleaned from an article on curealz.org:

 
Right now the hype around this possible “miracle drug” is fueled by the understandable desperation of millions suffering from dementia. If it could work, and if the drug is already safety-tested and approved by the FDA, why not use it as soon as possible?

REASON FOR CAUTION

There are a couple reasons to tone down the hype, though. My memory may be suffering some impairment, but I do remember other Alzheimer’s drug hypes that fizzled.
Remember Flurizan? “In mouse models, Flurizan™ reduced insoluble amyloid in the brain and improved spatial reference learning and memory” (from the Alzheimer’s Research Forum). In humans,

Flurizan worked by inhibiting enzymes that produce one form of amyloid, the sticky substance in the brain that many scientists believe is responsible for the disease. But there isn’t clear data to show that removing amyloid improves cognitive functioning; the hope was that Flurizan would provide the best human evidence to date. Its failure to deliver prolongs uncertainty about the wisdom of targeting amyloid to treat or even prevent Alzheimer’s.

And remember Eli Lilly? In mouse models of AD, the drug was able to lower brain Aβ concentrations and, in some cases, reduce Aβ plaque deposition (PubMed). In humans, Semagacestat blocked production of beta amyloid but made dementia worse.

In fact, on the side of caution, here is what a proposed guideline for Alzheimer’s research states:

…over 300 interventions have been investigated and reported to ameliorate pathological phenotypes and/or improve behavior in AD animal models. To date, however, these findings have not resulted in target validation in humans and successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical trials include the inability of mouse models to adequately recapitulate the human disease, variations in breeding and colony maintenance practices, lack of standards in design, conduct and analysis of animal trials, and publication bias due to under reporting of negative results in the scientific literature.

And then there’s the whole amyloid paradigm question. What if beta amyloid has nothing much to do with dementia? Some point out that regardless of amyloid markers, it isn’t until tau transport lines begin to break down and tangle that dementia shows itself. Do we chase recent studies that suggest tau jumps synapses to spread in the brain, or do we chase after an amyloid clearance mechanism? Do we do both? Do we chase down every bodily function whose breakdown leads to brain impairment, or do we accept, as the Myth of Alzheimer’s folks say, that “planning for possible cognitive impairment should be a part of everyone’s life planning”?

Consider the path of Alzheimer’s drug testing: the best time to administer Alzheimer’s blocking medication would be the early stages of the disease, also called MCI (mild cognitive impairment). But

only about 10 percent of people with MCI go on to develop full-blown dementia. That compares to about 1 percent of people without MCI, she said.
That means, of course, that 90 percent of people with MCI will never develop dementia.
There’s also the problem of reversion. In the current Mayo study, for example, one-third of the people diagnosed with MCI (or 12 percent per year) were later diagnosed at least once during the study as not having the condition. [Could it be] as Whitehouse claims, that MCI is so ill-defined that it is meaningless as a quantifier of dementia risk? (Cognitive Labs)

And if the best “treatment stage” of this ill-defined disease evades definition itself, what are we left with?

My gut tell me that the Cure Alzheimer’s Fund has a good model: raise private capital and study that which your gut tells you to study. Keep looking, keep testing, keep hoping. But tone down the pre-success hype.

What are your thoughts?