# Existing cancer drug clears Alzheimers plaques in mice **URL:** \ **Category:** Miscellaneous and Personal Stuff I Must Share\ **Created:** [March 11, 2012, 8:55am UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451 "2012-03-11T08:55:39Z")\ **Posts on this page:** 18\ **Page:** 1
**Author:** ![dzero](https://avatars.discourse-cdn.com/v4/letter/d/5f9b8f/32.png) [@dzero](https://boards.straightdope.com/u/dzero)\ **Post date:** [March 11, 2012, 8:55am UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/1 "2012-03-11T08:55:39Z")
Human trials to start in coming months. The drug is bexarotene, used for T-cell lymphoma for more than 10 years. The [article in Science News](http://www.sciencenews.org/view/generic/id/338355/title/Cancer_drug_may_have_Alzheimers_benefits) describes the unprecedented speed with which the drug works as well as the presumed mechanism. > [@](#): > > Cramer and her colleagues studied mice that had brains full of both kinds of A-beta. Just hours after mice began taking bexarotene, levels of the smaller kind of A-beta in their brains fell, reaching a 25 percent reduction after 24 hours. After 14 days of treatment, plaque levels fell by 75 percent, the team reports. > > “Nothing tested comes anywhere close to the speed with which existing amyloid is washed away by this drug,” says neurologist and neuroscientist Samuel Gandy of Mount Sinai Hospital in New York City. > > The drug works by changing the behavior of a cholesterol-carrying protein called ApoE by targeting a protein that regulates it. (ApoE is no stranger to Alzheimer’s researchers: People with a particular version of ApoE have a higher risk of the disease.) Earlier studies have found that ApoE shuttles A-beta out of the brain, acting, as coauthor Gary Landreth of Case Western calls it, as “a garbage disposal.” By improving ApoE’s ability to remove A-beta, “bexarotene helps Mother Nature do what she normally does,” Landreth says. > > Clearing out the A-beta from the brain had a profound effect on the mice’s behavior, too. Mice loaded down with A-beta have memory deficits and can’t learn new things as well as normal mice. After taking bexarotene for several days, animals showed a startling improvement in several different kinds of tests. ---
**Author:** ![Lochdale](https://avatars.discourse-cdn.com/v4/letter/l/edb3f5/32.png) [@Lochdale](https://boards.straightdope.com/u/Lochdale)\ **Post date:** [March 11, 2012, 4:32pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/2 "2012-03-11T16:32:17Z")
This is positive news. Any more info on the likelihood of success? ---
**Author:** ![Pops1963](https://avatars.discourse-cdn.com/v4/letter/p/9de053/32.png) [@Pops1963](https://boards.straightdope.com/u/Pops1963)\ **Post date:** [March 12, 2012, 4:46am UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/3 "2012-03-12T04:46:51Z")
wow again wow. Maybe this is a real breakthrough. ---
**Author:** ![Shmendrik](https://avatars.discourse-cdn.com/v4/letter/s/ee7513/32.png) [@Shmendrik](https://boards.straightdope.com/u/Shmendrik)\ **Post date:** [March 12, 2012, 5:01am UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/4 "2012-03-12T05:01:43Z")
[Maybe not.](http://healthland.time.com/2012/02/10/a-cancer-drug-reverses-alzheimers-disease-in-mice/) > [@](#): > > That doesn’t mean that Alzheimer’s patients should be asking their doctors for a prescription of bexarotene just yet. The mouse model of Alzheimer’s isn’t perfect. Mice don’t get Alzheimer’s the same way humans do. They build up amyloid protein in the brain, and those deposits form plaques that disrupt nerve function and affect learning and memory, just like they do in Alzheimer’s patients; but in mice, there is no progressive worsening of the condition resulting in the destruction of nerve fibers. Humans lose brain cells and suffer the buildup of detritus from a dying neural network. > > So it’s not clear yet whether bexarotene would have the same effect in an Alzheimer’s brain in which some of this destruction is already established. “I want to loudly and clearly say that this work has been done in mice,” says Landreth. “Let’s be very cautious in extrapolating forward to humans. We’ve fixed Alzheimer’s disease in mice a lot, and the translation to humans has been imperfect; in fact, it’s failed.” ---
**Author:** ![dzero](https://avatars.discourse-cdn.com/v4/letter/d/5f9b8f/32.png) [@dzero](https://boards.straightdope.com/u/dzero)\ **Post date:** [March 12, 2012, 5:12am UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/5 "2012-03-12T05:12:59Z")
> [@Shmendrik](#): > > [Maybe not.](http://healthland.time.com/2012/02/10/a-cancer-drug-reverses-alzheimers-disease-in-mice/) Thank you for bringing that up. There are a lot of things that look just stellar in vitro or in lab animals but later crash and burn when someone says ‘hey, I wonder what would happen if . . . oh, I don’t know, we injected some of this shit into some cute furry humans.’ However there might be a good chance that the part of the geneome encoding for the regulatory protein is conserved between mice and humans. It seems like the mechanism revolves around this single point, as opposed to many other diseases with more complex etiologies. If so, that alone should make it more promising. ---
**Author:** ![Nanoda](https://avatars.discourse-cdn.com/v4/letter/n/ce73a5/32.png) [@Nanoda](https://boards.straightdope.com/u/Nanoda)\ **Post date:** [March 12, 2012, 7:19am UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/6 "2012-03-12T07:19:10Z")
Fantastic! With an existing drug though, if enough people have been taking it, perhaps someone can just do the math on how many users _should_ have Alzheimer’s vs. the % that do? ---
**Author:** ![cerberus](https://avatars.discourse-cdn.com/v4/letter/c/71e660/32.png) [@cerberus](https://boards.straightdope.com/u/cerberus)\ **Post date:** [March 12, 2012, 12:19pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/7 "2012-03-12T12:19:37Z")
Or someone could do a proper human clinical trial. ---
**Author:** ![Ferret\_Herder](https://avatars.discourse-cdn.com/v4/letter/f/e47774/32.png) [@Ferret\_Herder](https://boards.straightdope.com/u/Ferret_Herder)\ **Post date:** [March 12, 2012, 12:36pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/8 "2012-03-12T12:36:29Z")
> [@cerberus](#): > > Or someone could do a proper human clinical trial. First doing a statistical analysis of current human users and their rate of developing Alzheimer’s might give a good justification for carrying out such a study. No one wants to spend millions (tens of millions, hundreds of millions) of dollars on a study that produces no results and unnecessarily exposes human subjects to the risks of taking this drug. I suppose if there is a definite reason to believe it works the same in humans - or if there isn’t a significant population of people who took the drug and lived long enough to get to the age where one might usually develop Alzheimer’s - then they might start limited human subjects trials sooner. ---
**Author:** ![lazybratsche](https://avatars.discourse-cdn.com/v4/letter/l/ba8739/32.png) [@lazybratsche](https://boards.straightdope.com/u/lazybratsche)\ **Post date:** [March 12, 2012, 1:22pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/9 "2012-03-12T13:22:42Z")
> [@dzero](#): > > Thank you for bringing that up. > > There are a lot of things that look just stellar in vitro or in lab animals but later crash and burn when someone says ‘hey, I wonder what would happen if . . . oh, I don’t know, we injected some of this shit into some cute furry humans.’ And unfortunately Alzheimers research has a few rather dramatic cases of experimental drugs that cure mouse models but don’t help humans at all. One dramatic failure involved a class of drugs that inhibited the production of amyloid proteins (gamma secretase inhibitors). These cleared the plaques in mouse models, and even resulted in cognitive improvements. In humans, these drugs also cleared the amyloid plaques, but they accelerated cognitive declines. _ **Clearing amyloid plaques, the supposed cause of Alzheimers, made the disease worse** _. ---
**Author:** ![Stelios](https://avatars.discourse-cdn.com/v4/letter/s/8dc957/32.png) [@Stelios](https://boards.straightdope.com/u/Stelios)\ **Post date:** [March 12, 2012, 1:27pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/10 "2012-03-12T13:27:55Z")
I was under the impression that Amyloid plaques are a _symptom_ of Alzheimers, and that the cause is deeper and has yet been discovered. Anyway, I always tune out as soon as I see the words “mouse models”. The vast majority of drugs which work on mice end up doing nothing for humans, and in some cases can make us worse. ---
**Author:** ![dzero](https://avatars.discourse-cdn.com/v4/letter/d/5f9b8f/32.png) [@dzero](https://boards.straightdope.com/u/dzero)\ **Post date:** [March 12, 2012, 2:12pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/11 "2012-03-12T14:12:20Z")
If you’re not a molecular biologist AND you happen to work in a particular area of research, it’s difficult to get a good handle on what some announcements actually mean. In this case, there might be more cause for optimism, but IDK. As I understand it, the plaques are actually a tangle of amyloid beta proteins that haven’t been trimmed (or something) by whatever enzyme takes care of that. For some reason this form is difficult to dispose of. In addition, it’s also very sticky and tends to clump. I don’t remember the exact mechanism that goes from that starting point to cell death, but I think most researchers belief it’s case of actual causation and not just correlation. Stelios’ comment about another peptide/drug/etc that did the same thing and produced the opposite result in humans is a bit of a downer, but that’s just how things work and why no matter how good the news seems, you don’t get too excited. ‘OMG, I’ve just cured cancer in mice!!!’ ‘Uh huh. Good for you. Take an extra hour for lunch today.’ ---
**Author:** ![Marley23](https://avatars.discourse-cdn.com/v4/letter/m/45deac/32.png) [@Marley23](https://boards.straightdope.com/u/Marley23)\ **Post date:** [March 12, 2012, 3:00pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/12 "2012-03-12T15:00:35Z")
> [@lazybratsche](#): > > And unfortunately Alzheimers research has a few rather dramatic cases of experimental drugs that cure mouse models but don’t help humans at all. Unfortunately that’s true. Maybe this will be an exception, but it’s going to take more time and research before there’s a substantial reason to think that’s the case. ---
**Author:** ![Raygun99](https://avatars.discourse-cdn.com/v4/letter/r/6f9a4e/32.png) [@Raygun99](https://boards.straightdope.com/u/Raygun99)\ **Post date:** [March 12, 2012, 4:45pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/13 "2012-03-12T16:45:24Z")
I, for one, welcome our imminent ape and/or shark overlords. ---
**Author:** ![lazybratsche](https://avatars.discourse-cdn.com/v4/letter/l/ba8739/32.png) [@lazybratsche](https://boards.straightdope.com/u/lazybratsche)\ **Post date:** [March 13, 2012, 2:15pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/14 "2012-03-13T14:15:19Z")
> [@dzero](#): > > As I understand it, the plaques are actually a tangle of amyloid beta proteins that haven’t been trimmed (or something) by whatever enzyme takes care of that. For some reason this form is difficult to dispose of. In addition, it’s also very sticky and tends to clump. I don’t remember the exact mechanism that goes from that starting point to cell death, but I think most researchers belief it’s case of actual causation and not just correlation. The hypothesis that amyloid plaques cause Alzheimers is still dominant, but it’s been taking a lot of hits recently. Frankly, the only place where there’s a clear causal link between plaque and disease is in certain genetic forms of early-onset AD. Most of the field has worked under the assumption that the more common forms of the disease have the same mechanism as the genetic form. And the animal models we use are basically engineered to have the early-onset genetic disease. It’s still entirely possible that plaques are a symptom of some other process in late-onset AD. One of the less-radical revisions of the amyloid hypothesis states that the amyloid plaques aren’t harmful. Rather, soluble amyloids might be the true cause of the disease, and plaques formation is an attempt to remove the toxic soluble proteins, and hold them in a “garbage dump” of sorts. In that case, plaque clearance would make the disease worse. The other major hypothesis is that AD might be caused by the aggregation of Tau protein that forms “neurofibrillary tangles”. ---
**Author:** ![DMark](https://avatars.discourse-cdn.com/v4/letter/d/e68b1a/32.png) [@DMark](https://boards.straightdope.com/u/DMark)\ **Post date:** [March 13, 2012, 3:48pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/15 "2012-03-13T15:48:45Z")
As others have mentioned, the transition from medical experiments on mice to humans is not always a perfect match. While I truly hope this particular research does advance therapy for Alzheimer’s, it is far too early to celebrate until human trials have shown any indication that it helps. On the flip side, after decades of successful medical research on mice, it won’t be long until the average age of a mouse is 207 years old. ---
**Author:** ![dzero](https://avatars.discourse-cdn.com/v4/letter/d/5f9b8f/32.png) [@dzero](https://boards.straightdope.com/u/dzero)\ **Post date:** [March 13, 2012, 5:55pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/16 "2012-03-13T17:55:55Z")
> [@DMark](#): > > On the flip side, after decades of successful medical research on mice, it won’t be long until the average age of a mouse is 207 years old. Sorta makes you wonder if that hasn’t been their plan all along. ---
**Author:** ![Hypno-Toad](https://avatars.discourse-cdn.com/v4/letter/h/b2d939/32.png) [@Hypno-Toad](https://boards.straightdope.com/u/Hypno-Toad)\ **Post date:** [March 13, 2012, 7:48pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/17 "2012-03-13T19:48:58Z")
> [@dzero](#): > > Sorta makes you wonder if that hasn’t been their plan all along. Those pan-dimensional creatures are sneaky. ---
**Author:** ![Ruken](https://avatars.discourse-cdn.com/v4/letter/r/f475e1/32.png) [@Ruken](https://boards.straightdope.com/u/Ruken)\ **Post date:** [March 13, 2012, 9:23pm UTC](https://boards.straightdope.com/t/existing-cancer-drug-clears-alzheimers-plaques-in-mice/615451/18 "2012-03-13T21:23:06Z")
> [@lazybratsche](#): > > _ **Clearing amyloid plaques, the supposed cause of Alzheimers, made the disease worse** _. It’s been 10+ years since I did any work in this area, but even then I remember some discussion that clearing the plaques might cause problems rather than solve them.