Last week, Dr. Roizen’s wife sent an email with the subject line: ‘Forward Alzheimer’s breakthrough.’ We’ve seen that type of headline before, which usually means BS (Bad Science).
But, a former caregiver of a relative with Alzheimer’s had just written us. This caregiver had gained 60 pounds during that process and developed type 2 diabetes, and wanted advice on reversing her diabetes.
Caregivers—especially caregivers for patients with severe difficulties like those in late stage Alzheimer’s—have to be beautiful.
There are few feelings in the world that surpass knowing you’ve helped someone. It feels good—and is good. So good, in fact, that the effect of altruisms big and small is similar to the so-called runner’s high (the rush of endorphins).
But unlike exercise euphoria, this rush can last a long time. The evidence: 90 percent of people who experience this high give their health condition a better grade than those who don’t. That benefit lasts a while, but the stress of 12 years (the average time from diagnosis to death in Alzheimer’s) of caring for a relative with Alzheimer’s is wearing, and can erode that benefit. And this isn’t a tiny problem—there are more than 10 million caregivers.
But back to that questionable email. While writing back to the caregiver, we opened it, despite our skepticism.
And we were blown away.
We couldn’t believe the study, and were so encouraged, that we immediately interviewed Paige Cramer, a Ph.D. candidate from Case Western Reserve and the study’s lead author. Her lab had been trying approaches to turn on the ApoE gene (which helps remove brain plaque associated with Alzheimer’s) and, in this one, she had made a major breakthrough.
This is how the study worked: Three different mice models of Alzheimer’s disease were treated with Bexarotene, an approved FDA drug (usually used for cancer) given by gavage (pushed down into the stomach of the mice like you’d take a pill); and their beta amyloid plaque melted away. More importantly, the mice had a magnificent return of cognitive function (or at least as best as that can be tested in mice). This was based on a predicted response by the drug in turning on the ApoE gene.
We may find out very quickly if this works in humans, as we already know the toxicity and way to dose this drug. But let’s go back to the start.
Your brain cells put out waste products, or trash, in the form of beta amyloid protein. Normally you have a garbage truck in the form of ApoE that comes along and picks up that trash. If one of the ApoE genes you get is a mutant or dysfunctional, your risk of Alzheimer’s disease goes up about 30 percent. If you have two, it goes up more than 60 percent. So improper functioning of this gene leads to Alzheimer’s.
These mice were designed to produce lots of beta amyloid. When the Case investigators gave this drug to the mice it turned on the ApoE expression to make more. It put more trucks to pick up the beta amyloid waste product; thus less beta amyloid remained in the brain to stimulate inflammation, and consequently less brain cell destruction. The researchers noted that 25 percent of beta amyloid disappeared in the first six hours—and 75 percent of it in three days! But more importantly, brain cognition, returned quickly and special sense returned in 20 days.
If you extrapolate these numbers in human studies, that would be similar to 75 percent of plaque disappearing in 100 human days.
OK, what’s the hold up for trying this in humans? Very little, actually. The questions would be: what are the side effects of this drug and is there enough of the drug available? A small company makes Bexarotene for a specific cancer diagnosis. In some people, it causes liver, thyroid and blood cell problems, birth defects, kidney failure and some other unpleasant things. Most Alzheimer’s patients are past their procreating years and don’t have to worry about birth defects.
As of 2010, Alzheimer’s is predicted to affect about five million people in in the U.S., but increase to more than 12 million in 2050, with worldwide prevalence going from about 25 million cases to over 100 million in 2050. Its cost in the U.S. for caring for such patients will increase from $170 million to over a trillion in 2050 (not counting the time value for 30 million family caregivers expected in 2050).
With this breakthrough, we hope we’re one step closer to see Alzheimer’s victims (and their caregivers) saved from this horrible disease.
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