A skin cancer drug can improve Alzheimer-like symptoms in mice engineered to mimic the condition, it has been widely reported.
Many national newspapers have covered the news, which is based on aninal tests involving the drug bexarotene (brand name Targretin , which is currently only used to treat a rare form of skin cancer. This drug was given to mice that had been genetically engineered to develop a condition similar to Alzheimer’s, and in a short space of time the mice showed lowered brain levels of a key protein called beta-amyloid. Beta-amyloid is the substance that forms the protein plaques in the brain that are characteristic of Alzheimer’s. The researchers also observed post-treatment improvements in the brain function of the mice – for example, they were better able to build nests and remember the way through a maze.
Although this research is in animals and there is limited direct application to humans at the current time, these early findings do show some potential for further research. Notably, the drug had a rapid effect on amyloid plaques that are characteristic of Alzheimer’s, and the fact that drug is currently licensed means it will have undergone safety regulations for its current use. That said, there are no guarantees it will prove as safe or effective in people with Alzheimer’s.
At the current time no tests have been carried out in humans with Alzheimer’s, only an animal model of the disease. The research will undoubtedly be of interest to researchers, doctors, and patients and their families, but it is far too early to suggest that this could be a cure for Alzheimer’s.
Where did the story come from?
The study was carried out by researchers from Case Western Reserve University School of Medicine, Cleveland, and other institutions in the US. The study was supported by a number of research funding foundations, including the Blanchette Hooker Rockefeller Foundation, Thome Foundation, and the Roby and Taft Funds for Alzheimer’s.
The study was published in the peer-reviewed journal Sciencexpress.
BBC News gives accurate coverage of this study. The Sun, Daily Mail and The Daily Telegraph featured slightly optimistic headlines, but their articles generally do make it clear that this was a study in mice and give good accounts of the research.
What kind of research was this?
This was animal research aiming to investigate the effects of a drug called bexarotene on a mouse model of Alzheimer’s disease.
Bexarotene activates a receptor on the surface of cells that is known to be involved in triggering the production of a protein called ‘apolipoprotein E’ (ApoE . The ApoE protein is involved in the breakdown of soluble beta-amyloid, a protein that builds up to form the characteristic insoluble plaques seen in the brains of people with Alzheimer’s.
All humans carry a gene containing the code for producing the ApoE protein, but some people carry a particular variant of the ApoE gene known as the ApoE e4 allele. People carrying this variant are known to be at increased risk of developing Alzheimer’s disease, and carrying this variant seems to be associated with the build-up of beta-amyloid plaques in the brain. Therefore the researchers were interested whether a drug that increases production of ApoE could potentially have an effect on the build-up of beta-amyloid in the brain. To explore this possibility they decided to test the drug in mice with Alzheimer’s-like symptoms, looking at whether it could reduce their their beta-amyloid levels and improve their cognitive performance.
What did the research involve?
The researchers used various different genetically engineered mouse models of Alzheimer’s in their experiments. The researchers carried out a number of tests to assess the effects of bexarotene on soluble beta-amyloid in the fluid surrounding the brain, insoluble beta-amyloid plaques in the brain, and cognitive performance of these mice.
The mice were administered oral bexarotene for three, seven, nine, 14, 20 or 90 days. These mice were compared with similar mice that did not receive bexarotene. The researchers looked at mice of three different ages: two months, six months and 11 months in order to look at the effects of the drug when given to mice at different stages of their Alzheimer’s-like condition – the older mice having more beta-amyloid protein build-up.
The mice in models of Alzheimer’s display impairments in their performance in several tasks: navigating a water maze (an indicator of cognition ; nest construction (an indicator of social behaviour ; fear response to placement in a shock chamber; and sense of smell. In a sample of mice the researchers tested performance in these four areas after administering the drug.
After the treatment periods the mice’s brains were examined to look for any changes.
What were the basic results?
The researchers found that administering a single dose of bexarotene gave a rapid reduction in levels of soluble beta-amyloid in the fluid surrounding the mice’s brains. There was a 25% reduction within 24 hours and this reduction was retained for over 70 hours. Up to 84 hours after treatment there was a return to pre-treatment levels of soluble beta-amyloid.
In six-month-old mice treated with bexarotene, insoluble beta-amyloid levels in the brain were reduced by 40% after 72 hours. When bexarotene was given to mice for longer periods of time they found a sustained reduction in beta-amyloid throughout the treatment period. They found comparable effects of the drug when testing in older, 11-month-old mice with greater beta-amyloid build-up.
The drug also improved the cognitive, social and sensory deficits of the mice:
- both six-month and 11-month-old mice treated for seven days showed improvements in fear conditioning; the six-month old mice also showed improvements in fear conditioning with 90 days of treatment
- performance in the water maze improved after 20- and 90-day treatment periods
- nest construction behaviour was restored after 72 hours of treatment
- ability to sense odours was restored by three days of treatment
How did the researchers interpret the results?
The researchers conclude that activation of the receptor involved (the retinoid X receptor through use of bexarotene helps to clear beta-amyloid build-up in mouse models of Alzheimer’s and gives a rapid reversal of the associated cognitive and neurological deficits.
Conclusion
This animal research has demonstrated that bexarotene can have a positive effect in clearing the build-up of the characteristic beta-amyloid protein plaques and improving cognitive impairments in mouse models of Alzheimer’s. Bexarotene (brand name Targretin is an anti-cancer drug that is currently licensed specifically for the treatment of a rare type of skin cancer called advanced cutaneous T-cell lymphoma.
Although this research is in animals, and therefore has a limited direct application to humans at present, these early findings do present some genuine potential that needs further research. There is bound to be great interest in the finding that the drug seemed to have an early effect on the amyloid plaques characteristic of Alzheimer’s, particularly as the study involved a drug that is already licensed for use in a specific, rare type of cancer (advanced cutaneous T cell lymphoma . Given its existing use, there may be the possibility of earlier testing in humans than there would be if this were a completely new chemical in development, which would have completely unknown health and safety effects.Nevertheless, this drug has not yet been tested in humans with Alzheimer’s, and results from such studies will be needed before we know for certain whether it is also helpful in humans.
Better treatments for Alzheimer’s in humans are needed, and research such as this is is an important early step towards achieving this goal. While it is far too early to say whether this drug could be a cure for Alzheimer’s, at least in the context of this early research the drug has marked itself out as a clear candidate for further exploration.
Links To The Headlines
Alzheimer's brain plaques 'rapidly cleared' in mice. BBC News, February 10 2012
Skin cancer drug 'reverses Alzheimer's'. The Daily Telegraph, February 10 2012
Skin cancer drug 'clears Alzheimer's protein from the brain'. Daily Mail, February 10 2012
Does skin cancer drug offer Alzheimer's hope? Channel 4 News, February 10 2012
Links To Science
Cramer PE, Cirrito JR, Wesson DW, et al. ApoE-Directed Therapeutics Rapidly Clear ?-Amyloid and Reverse Deficits in AD Mouse Models Science. Published online February 9 2012
The "Arsenic Prevention and Protection from Lead Exposure in Juice Act of 2012" or "APPLE Juice Act of 2012" is in response to a Consumer Reports investigation that found levels of arsenic and lead that exceeded the federal standards for drinking water in 10 percent of apple and grape juice samples tested in New Jersey, New York and Connecticut.
As the lawmakers note, both arsenic and lead are known to affect brain development in children. Both toxins are pervasive in the environment -- both naturally occurring and the result of pesticide use, emissions and other industrial and agricultural chemicals. In both cases, the federal government has set a safety threshold for drinking water but not for juice.
The APPLE Juice Act would require that FDA establish standards for fruit juices within two years.
"The unacceptable levels of arsenic and lead in juices currently sitting on shelves at the supermarket present a danger for our children and their health," said Pallone. "Setting basic standards for arsenic and lead in products whose consumers are primarily children is not only the right thing to do, it will help give parents the peace of mind that the juices their children drink daily are safe."
DeLauro, who often takes a lead on food safety issues in the House, said she was proud to join Pallone in introducing the bill.
"We must ensure that the juices our children drink are safe, particularly when 70 percent of the apple juice we consume comes from China," said DeLauro. "It is our job, and the FDA's job, to ensure the health and safety of the American people. This legislation will help to make that happen."
As the lawmakers noted in their announcement, though pediatricians often recommend that children limit their daily juice intake, 35 percent of children under five drink more juice than recommended.
"This bill will go a long way in protecting the public, especially children, from being exposed to these toxins. We're grateful for this effort to ensure the public's health and safety are protected," said Ami Gadhia, senior policy counsel for Consumers Union, the policy and advocacy division of Consumer Reports.
The bill comes just a few months after there was heightened public awareness about arsenic in the fall. Popular TV personality Dr. Mehmet Oz reported that some top-selling brands of apple juice were laced with high levels of inorganic arsenic. As Food Safety News reported then, most news reports were skeptical about the public health risk, especially after the FDA called the claim irresponsible.
Consumers, nonetheless, were concerned.
A few months after the Dr. Oz story aired, Consumer Reports released testing results that seemed to back up the claim that a small percentage of apple juice might have higher levels of inorganic arsenic than previously thought.
Consumer Reports tested 88 samples of apple juice and grape juice purchased in three states and found that 10 percent had total arsenic levels exceeding the federal standards of 10 parts per billion (ppb for arsenic in drinking water, and that most of the arsenic "was the type called inorganic, which is a human carcinogen." The tests also found that 25 percent of the juice tested had lead levels higher than the 5 ppb limit for bottled water.
The FDA says its "level of concern" for heavy metals in juices is anything above 23 ppb. The agency maintains that there is no threat to public health but testing has been stepped up.
"With respect to arsenic in apple juice, we're looking hard at whether we need a different, more stringent number to guide our action in regard to arsenic in juice," said Michael Taylor, Deputy Commissioner for Foods at FDA, in a recent interview with Food Safety News. "We need to be vigilant on these issues and I think we're making the right efforts to do that."
In light of the recent anti-aging breakthroughs (namely scientists working tirelessly towards halting the aging process and a pill to prevent gray hair , it begs the question: is “aging” the new medical condition to fear? Perhaps an over-the-top question, but most women I know (and plenty of men talk about aging as if it’s a major illness. Honestly, the way some of my girlfriends talk about wrinkles you’d think they had a degenerative disease of some sort.
These days, people are flocking to plastic surgeons like moths to a flame – all in hopes they’ll stop the proverbial clock. In fact, in 2010, 9.5 million people had cosmetic surgery. That's up 9% from 2009, with breast augmentation and liposuction topping the list of procedures. Our fixation with youth is rampant, as the thought of age (such an ugly word has become a stigma. It’s left me questioning my thoughts and character on the matter and, despite my best efforts, my virtues don’t seem to fall into the “grow old gracefully” bucket…
Is Aging Gracefully For Sissies?
After much thought and soul searching, I’ve concluded that I’m on the fence when it comes to this topic. While my moral character tells me I should consider my smile lines a badge of a happy life and my crows’ feet a brand of years of laughter, my vanity gets the best of me as I scrutinize my wrinkles in the mirror. (I’ll spare you my rants on the toll gravity has taken on areas
below
my the neck. But instead of fretting over signs of aging, shouldn’t we be grateful we’re healthy and able? Not an easy task with titles like crows’ feet, turkey neck, old lady hands, cellulite, and age spots. It’s all too easy to get sucked into the frenzy.
Related:
The Anti-Aging WORKOUT
Eternal Youth?
So, will scientists soon find a way to halt the aging process? It certainly sounds promising. In a study reported in the journal of
Nature
, scientists gave mice a drug that “flushed out” the retired cells (that accumulate naturally with age . Post treatment, the mice suffered from less fat loss under the skin (which keeps skin youthful , had fewer eye cataracts, and less muscle loss. While the research is still in early stages (read: you might be a senior citizen by the time it’s on the market , scientists are confident they’ll create a successful anti-aging cure. And if that’s not enough to lift your anti-aging spirits, this will be: they’re also working on a pill to prevent gray hair. After all, if science will soon allow us to stop the aging process, then we most certainly couldn’t have gray hair giving away our real age, now could we? L’Oreal says it is hard at work creating
this cosmetic breakthrough, and expects it to be on the market by 2015. In short, this magical pill will stop “oxidative stress” (fancy words for the process by which follicles turn hair gray . The downer? If you’ve already got salt n’ pepper hair, you’re SOL.
So, what’s your take? Should aging be considered a disease? Or are we misguided in our unwavering quest for eternal youth? And if we do achieve the cure for aging, what will Mother Nature do for a living? (Starbucks barista? Wal-mart greeter?
I’ll be the first to admit (through gritted teeth I have definitely been “bitten” by the fear of aging (insert self-reproach here . Well then, bring on the snake oils…
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