Science Brief: Early Work On A Nanoparticle Aimed At Treating Alzheimers Disease
Alzheimer's is a neurodegenerative disease which is characterized by cognitive decline and the loss of ability to form short-term memories. The disease gradually progresses to affect all facets of life and is incredibly sad to watch helplessly as a loved one goes through the progression. This disease has struck my own family and I can imagine that many of you have seen what I have.
Biochemically, Alzheimer's is thought to occur at least party due to the accumulation of thick waxy plaques in the brain comprised of a protein called amyloid beta (Abeta). There have been (and are still) numerous research projects looking into better understanding the accumulation of this protein plaque and to develop drugs which would work to either prevent it from accumulating more or break up what has formed.
Today let us briefly discuss some work published in the journal Nature: Scientific Reports titled "Chronic treatment with a smart antioxidative nanoparticle for inhibition of amyloid plaque propagation in Tg2576 mouse model of Alzheimer’s disease". The first person to reply to this post stating "Monkey Monkey, Tree, Look At Me, I'm talking Nonsense!" Will be sent 2 SBD. In this work the authors were studying a new nanoparticulate compound with reducing properties that could potentially allow it to break down these Abeta plaques.
Briefly Tell Me About This Nanoparticle
The nanoparticle which they abbreviate (RNPN) is actually a long polymer comprised of the compound (poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)aminomethylstyrene]), this compound has a water loving part (poly(ethylene glycol) and a water hating part (the rest of it). This results in the polymer forming what is known as a mycelle which basically is a ball like structure where a bunch of the water hating tail groups point inward together, leaving the water loving part to be in contact with water on the outside of the ball. The compound breaks apart under acidic conditions (like the stomach) which allows it to be absorbed by the body, where it can again reform (our blood is non acidic). [2]
This compound has reductive properties (it can gobble up radical oxygen species, and acts as an antioxidant), and has previously been shown to have antioxidant activities in the brains of some mice! [3] Knowing this, the authors here wanted to test whether it might be useful against Abeta plaques.
What Did They Find?
The researchers were using a transgenic mouse which had the Alzheimer's causing Abeta protein overexpressed (meaning they artificially induced the protein to be in these mouse's brains in high concentrations). These mice have cognitive difficulties just like humans with Alzheimer's. Next they confirmed that their nano-particle could get into the brains of these mice as had been previously shown for a different variety of mouse, and saw that yes it could. Okay step one, check, compound gets to the mouse brain...but does it do any good?
In this first test, mice were acclimated to a box containing an object in a particular position (in one corner). The mouse was removed, the object was moved, and the mouse was placed back in. Now mice are pretty smart, and they notice when something has changed in the environment and will go explore what has changed. Well unless they have alzheimers, then they can't remember and no longer spend time exploring. This test reports the difference in time that the mice spent exploring the change in object location allowing us to see what effect the compound had.
The important part to compare is first the wild type (non Alzheimers mice) vs the AD + Water group (alzheimers mice given water to drink). We see that the wild type mice spent much more time exploring the objects new location then the alzheimers mice (which spent no time... I guess they forgot). Next look to the bar showing AD + RNPN this is the alzheimers mouse treated by their nano-particle. You can see that the nanoparticle greatly improved the mice's curiocity for the objects new location vs the AD + water group!
Other Article Observations (The "Brief" Rundown!)
- RNPN improved the alzheimers mice's abilities to navigate their way to an invisible platform in a pool of water in the "Morris Water Maze test."
- Expression of proteins indicative of oxidative stress (known to be high in the alzheimers mouse) were significantly reduced upon treatment with the RNPN nanoparticle.
- Decreased levels of both forms of Abeta (1-40) and (1-42) were observed in the brains of the alzheimers mice given RNPN treatment. (1-42 is the form of the protein that typically forms the aggregate, seeing a reduction in the amount present in the mouse brains is very promising).
Conclusions
The authors report that their nanoparticle (RNPN) which has the ability to break down in the stomach, easily get absorbed, re-assemble and get to the brain. Also has antioxidative properties, reduced the amount of amyloid beta in a mouse model, as well as helped those mice regain some cognitive functioning. A very interesting and promising piece of work!
Sources
- https://www.nature.com/articles/s41598-017-03411-7
- http://pubs.acs.org/doi/abs/10.1021/bc900214f
- http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126013
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If you like this work, please consider giving me a follow: @justtryme90. I am here to help spread scientific knowledge and break down primary publications in such a way so as to cut through the jargon and provide you the main conclusions in short (well compared to the original articles at least!) and easy to read posts.
Monkey Monkey, Tree, Look At Me, I'm talking Nonsense!
Is that still up for grabs? lol :)
Hey someone ACTUALLY read it!
Edit: Sent 2 SBD.
Yep :) . By the way i'm half way through it. Its pretty good so far.
Well thank you :)
For these shorter posts it's tough to balance any sort of brevity while maintaining some detail. Still working on how to best accomplish this.
Yes, I know, but you're getting pretty good responses, which must feel satisfying.
I have had a few posts that have generated some really great and interesting discussion. That is honestly the best part. I feel like a big part of the struggle to inspire this is my own limitations in writing. So yeah, it's wonderful when I get awesome responses! That is super encouraging that I am on the right track as I keep learning how to blog. Science I can handle, effective communication, that has a steep learning curve :)
Thx I have two cases of Alzheimer's in my family
Ugh, I am sorry to hear this.
Are dimentia and alzheimers the same thing or caused my similar thing? I have heard both terms am not sure of the difference
Dementia is any disease of the brain which reduces ones ability to think. It can be caused by a variety of factors, even things like arterial hardening and reduced oxygen flow in the brain.
Alzheimer's disease is one such cause of dementia (and a very prominent one) with very specific causes (some of which I mentioned above in the post!). So in short, all Alzheimer's is dementia, but not all dementia is Alzheimer's.
Great idea to try and make this easier to access. My Mum has vascular dementia (not quite the same but the prognosis is similar) but I do spend quite a bit of time online sussing out the latest research on her condition as her daughter and carer. Thank you and keep up the good work.
Yep, vascular dementia is indeed a bit different (brain oxygen/blood flow restriction). Sorry to hear about your mom, she is in good hands if you are putting in the extra effort to better understand the condition. Thanks for giving this a read, glad you were able to get something out of it.
Yep, online when I'm searching for medical info my motto is 'if it isn't peer reviewed move on'... the problem with that is its usually very difficult to read. Thanks for your kind words.
That's a good motto. There are also good breakdowns of primary literature. Scientific American does nicely. There are many others, as well, trying to cut through the jargon of science writing, and also get passed the dryness and distill out the important factual tidbits. So hopefully your researching doesn't have to happen entirely on pubmed.
I hear ya! Pubmed has become a bit of go-to I've need to do extensive research so I'm getting quite a bit of practice and it has been very helpful to have knowledge on board when making treatment decisions. So I'll be back...
Great Post...Thanks for sharing this research paper. I can see the beauty of this posts Being the Medicine guy...Alzheimer right now is the common disorder of developed countries occuring in the later years of life. A lot of research is being done about the causes and how to treat Alzheimer's. Still much is needed to be done in this field. Thanks Again for the Informative Post. A doctors' upvote.
Thanks for reading! Yeah there is still so much that isn't well understood about the biology of this disease. For instance is Abeta really the best target? Just how relevant is the Tau protein? There are a variety of conflicts in the literature which I hope will gel into a more concrete story in the near future.
As usual the pharmaceutical companies will buy the patent and never use it because curing diseases does not bring anything
Not at all true (at least not for all pharma, perhaps it is more true for the larger pharmaceuticals, but there are plenty of smaller ones that work on cures... like mine). This treatment would be pharma's dream anyway. The nanoparticle would need to be continuously taken to prevent the amyloid beta from re-aggregating. That has all the signs of making profits.
true ,as it happened in algeria a cure of diabeties was found by a biologist called D ziibet last year ;he was attacked by media and almost been killed now he has sold the medecin to a turkish company
Yeah, right. Uh huh.
if you dont believe me you can google it
Very interetsing !!!
Thank you for reading ;)
Dam someone beat me to "Monkey Monkey, Tree, Look At Me, I'm talking Nonsense!". Oh well, I wonder how long before human trials, it can't come soon enough!
At minimum at least 5-7 years probably. If pharma picks it up they have to go through a boatload of toxicology studies before a human clinical trial can be initiated and those take forever...
That would be my guess, pity though, it will be too late for a lot of people.
Hey - very interesting article. I am also interested in nanotechnology. Lateley I read an article in which they described how to destroy cancer cells using nanoparticles and MRI fields. Very interesting stuff going on.
If you are interested in groundbreaking science stuff: Check out CRISPR Cas 9
I've worked with Cas 9 :)
Cool stuff - what do you think, will there be use of it in treating deseases within a reasonable timeframe? (Let's say within the next 5-10 years)? I know that China already started human trials and the USA is about to do so as well in 2017
Human clinical trials on this compound?
Yep - in China they already treated people with lounge desease - maybe I will make an article about that ;)
To use it for a radical oxygen sponge, in chemo therapy correct? Not for potential alzheimers treatment.
Don't know about Lounge disease, yeah you should definitely make a post :D