Before going too far into this new study, non-scientist readers should remember that every year basic research produces hundreds of promising leads that for whatever reason don’t pan out. Either the proposed treatment has too many side effects, it doesn’t work as well as something already on the market, follow-up work discredits the original report or the treatment doesn’t work when translated from mice to humans. As a general rule exciting lab results should raise an eyebrow but we should hold off on changing our lives until the clinical trials are in.
That said, keep an eye on new results from a team at MIT:
Scientists found mice with a similar condition to Alzheimer’s were able to regain memories of tasks they had previously been taught.
A team at the Massachusetts Institute of Technology found two methods – brain stimulation and drugs – both worked.
[…] After six weeks with the brain disease, the mice were no longer able to remember how to perform these tasks.
Some of the mice were then placed in a more stimulating environment with toys, treadmills and other mice.
The playground mice were able to remember the shock test far better than the mice in other cages. They were also better at learning new things.
Scientists then tested a class of drugs called histone deacetylase, or HDAC, inhibitors on the mice.
These also improved memory and learning, similar to improvements made by environmental stimulation
Also reported in the Washington Post, which emphasizes the treatment’s potential to recover lost memories.
HDAC proteins reduce gene expression by tightening the interaction between histone proteins and DNA. Inhibiting these lifts the block on silenced genes and increases overall gene expression, although it remains unclear how exactly gene silencing relates to the protein plaques that cause Alzheimer’s disease.
Although none of the reports I have found identify the drug (anybody?), it struck me that this class of drug alost exactly counteracts a red wine-related polyphenol called resveratrol, a drug that should sound familiar to frequent readers of this blog. Although none fo the reports have made the jump from lab animals to humans, resveratrol and related polyphenols have shown promising results in preventing cancer, decreasing infectious diseases, extending lifespan, increasing stamina and most intriguingly, increased mental agility in rats. If HDAC inhibitors fight Alzheimer’s disease, and resveratrol almost directly counteracts the effects of HDAC inhibitor drugs, does that mean that resveratrol makes Alzheimer’s disease more likely? Why would resveratrol-like polyphenols increase mental agility and at the same time almost the exact opposite drug fights Alzheimer’s?
This work lies outside my personal expertise so all that I can offer is provocative questions. But the odd contradictions here suggest that something weird is going on, and a lucrative prize waits for whoever figures it out.
Hyperion
quick, get some for Abu before he testifies again.
but maybe you have to want to remember
empty
From what (very) little I know HDAC downregulates expression of all kinds of genes – not just those related to dendrite formation and synaptic marker proteins. So if we inhibit HDAC should that not result in all kinds of proteins being expressed that “normally”should not be? I would think the side effects would be absolutely humongous so Tim’s caveat
is very appropriate.
Tim F.
empty,
Yes, widespread upregulation of gene expression is a great first step towards cancer. Among other potential problems almost too numerous to list.
scarshapedstar
Well, as I recall, recent research indicates Alzheimer’s is caused by protein aggregation that leads to plaques and all sorts of bad things. So, if you can stop the “bad” protein from being translated (along with what else?) then you may be able to get rid of it.
DougJ
Maybe if didn’t spend so much damn time killing Blastocyst-Americans and spent a little more time studying mice, we’d be able cure a disease every now and then.
Gold Star for Robot Boy
Alzheimer’s is the cruelest disease imaginable.
The Other Steve
Did you see the new research linking cancer and Vitamin D deficiency?
The study showed a 60% reduction in cancer amongst a group of women taking Vitamin D supplements, compared to their control group.
DougJ
Yes it is. An older friend of mine died from it a few years ago and seeing her near the end for a few days made my heart go out to people whose parents or spouses have the disease.
Quiddity
I always find that my memory improves after several weeks in an environment consisting of toys, treadmills and other mice to play with.
Krista
It’s definitely one of the cruelest, particularly for the family members and friends to have to watch.
I do think that the absolute cruelest is ALS, however.
My great-uncle had ALS, and the thought of him being completely lucid while trapped in that body was just horrific. My nanny, on the other hand, has Alzheimer’s. It was bad when she’d have moments of lucidity and get really upset about what was happening to her — that was really hard. But she’s now in her own world, and really doesn’t pay too much attention to what’s going on, and seems to be relatively content.
I do agree that brain stimulation is vital. My mom has made sure that my nanny’s had a steady stream of visitors and caretakers, and they’ll read to her, and she maintained much of her memory and her mind long after the doctors said she’d have lost all of that.
Hunter
A good, but long explanation is here. My own (slightly) more brief understanding follows. The plaque associated with Alzheimer’s apparently kills neurons and severs neural connections. If this plaque can be cleaned out, the damage still will have been done, as with any other disease that causes similar damage. The memories still will have been lost.
(Sidenote on memory: it’s not that some dead neuron had a memory in it, but rather some connected group of neurons encoded the memory in the structure of the interconnections of the group.)
After damage is no longer occuring, the authors of this paper found that by upregulating the expression of certain genes, they could coax the neurons that hadn’t already been killed into reestablishing some of the lost connections. They were effectively growing like they were much younger neurons (cue cancer comparison), but they somehow managed to grow back in enough of the same way to preserve (something like) the original memory.
This is still blue sky science, but it’s the kind that adds an important piece of knowledge to our collection. Later, when we can manipulate gene expression at a more fine-grained level (so as not to accidentally cause cancer, etc…), and when we can consistently halt the progression of diseases like Alzheimer’s, we now know we will even be able to (at least partially) reverse the memory loss.
And Huntington’s is the cruelest disease.
christian gocke
The HDAC inhibitors used in the recent Nature paper by Fischer et al. inhibit a different class of HDACs (class I/II) than the ones that Resveratrol activates (Sirtuins or Class III). Therefore, accelerated aging is not such a worry. Additionally, HDAC inhibitors similar to the ones that were used in this study are already being used in clinical trials to treat cancer and appear to be relatively safe up until now (at least some of them are safe. there are many inhibitors out there that have differing specificity towards the 11 class I and class II HDACs in humans). The idea behind using HDAC inhibitors for cancer treatment is that many tumor suppressors are repressed in cancers, and this repression can be rescued often with HDAC inhibitors.
Pooh
Cue Paul L. drive-by linking in 5…4…3…
Anthony Loera
I agree with this, but if you have something that prevented plaque in the first place, wouldn’t you ask those prone to Alzheimer’s to take it as part of a regiment?
Anthony Loera
http://www.RevGenetics.com – R500 Resveratrol