Molecular 'Piggyback Ride' Carries Alzheimer’s Protein Into Brain [potential breakthrough]

University of Rochester Medical Center ^ | 6/24/2003

[B.Bumbleberry]

Someone with better background can judge whether this represents a true milestone. It appears so from a lay perspective. Wonder what the "anti-RAGE" and "soluable RAGE" chemicals consisted of.

[lepton]

It's also interesting why RAGE molecules would be produced by the cells in the barrier layer, and what is supposed to be happening, but isn't, when the molecules are disabled.

[RippleFire]

bump

[SierraWasp]

"...get through by riding piggyback on a much larger molecule, called RAGE."

I don't know, but I'll bet that punk-rock band will have to change it's name from "Rage Against the Machine," to "Rage against the Molecule!"

No kidding... This is a great breakthrough!!!

Just wish it had been found in time for Ronaldus Magnus!

[The Old Hoosier]

[Grampa Dave]

Lets hope that this works out.

Years ago a neurologists I knew, made an interesting comment about a large % of patients with Alzheimer’s that he had seen and was seeing.

He said that they had incredible immune systems. They were the ones who seldom had colds, viruses and pneumonias were very rare in their lifetime before Alzheimer’s. He wondered if their immune system hadn't turned against them in areas of the brain. He was one of the first to theorize that MS was due to an over response of the immune system on the myelin sheathes.

Hopefully we will make some great breakthroughs here.

[CDHart]

From the article: "Finally, we learned that when we block the flow of amyloid beta over time, the brain substantially rids itself of amyloid beta and the amyloid plaques shrink dramatically. "

Looks like maybe it's reversible, if I'm understanding this properly? What a blessing that would be. I'm an accountant in a skilled nursing facility, and we have a "secure" unit for Alzheimer's/dementia residents. Sad thing.

Carolyn

[RonF]

B.S. in Biology and M.S. in Biochemistry with an emphasis on protein chemistry:

Yes, I'd say that this is definitely a huge milestone. Understanding how the beta amyloid got transported past the blood-brain barrier is big in itself. Coming up with a method for inhibiting it is even bigger.

I haven't looked up RAGE yet, but judging by it's name it's going to be a complex glyco-protein (a protein molecule with pieces of carbohydrate attached, both having specific makeup and structure). Such things can be synthesized once the structure and sequences are completely determined (grunt work, but highly doable). Or, they can find a way to genetically engineer some other organism to produce it biologically. We're taking expensive but effective therapy.

[Cicero]

It sounds very promising. There are still questions to be answered. Does it have side effects? Playing with a protein that governs transfers through the body/brain barrier is obviously a delicate matter. It might affect other transfers or balances, perhaps in some subtle, long-term way. But still very promising, especially for people who are clearly Alzheimer's prone.

[B.Bumbleberry]

Well, they already applied an "anti-RAGE" molecule and a "soluable RAGE" molecule, so they already seem to have the chemistry down. Just what these are is what interests me.

My mother died of Alzheimer's, Cindy. A horrible fate for a family, who suffer more than the person with the disease as they watch their loved slowly disappear.

[B.Bumbleberry]

Sorry Carolyn. I meant you, not "Cindy". My brain is slipping. Hope it's not you know what.

[cajungirl]

This is exciting. And if you have early altzheimers, you may be willing to take a chance on something with long term effects. This is very hopeful. For a long time the beta amyloid and other substances, tau protein, have been known as part of the process of developing plaque and tangles in the brain. It may be that the amyloid is the most important. And possibly reversible. This would be an incredible thing, hope it comes soon. Think of the effects.

[RonF]

The anti-RAGE molecule could have been developed experimentally, by either taking RAGE molecules isolated from mice, inducing mice to make antibodies to them, and then using those antibodies to affect the RAGE molecules, or else by simply testing simple molecules until they found one that blocked the beta-amyloid from binding to RAGE. The "soluble" RAGE could have been created by treating the RAGE molecule with an agent that removed the lipophilic moiety of it without understanding exactly what portion was removed or what the extent was.

Both of which are a ways from understanding the exact sequence and 3-D structure of the protein, the sequences of the carbohydrate portions, and where on the protein the carbohydrate portions bind. All of which will have to be understood if the molecule is to be synthesized, especially if that synthesis is chemical, not totally biological. And it would be quite helpful to understand the location and chemistry of the beta amyloid binding site as well. As a previous poster stated, we don't know what other effects administering RAGE, or the soluble RAGE, will have on other blood-brain processes. There's a lot of biochemistry yet to be done to take this out of the lab and into a production facility.

But this is a wonderful start, and Alzheimer's is no orphan drug situation. An effective therapy for this is something that the drug companies will jump all over.

[cajungirl]

HMMM,,,I wonder what drug co funded the research if any did,,,if so, now is the time to buy!

[cajungirl]

NIH funded it,,drats!

[RonF]

Get yourself a copy of the July 1 issue of Nature; there should be information in there about where the funding came from. If a foundation is named, you might have to drill down some.

There may be no drug company funding this at all. It could all be funding from NIH, the school, and various foundations.

[kms61]

And I certainly can't see any reason why someone wouldn't want to take a chance on it. Whatever the side effects might be, that surely can't be worse than Alzheimers.

A former girlfriend's mother contracted a disease similar to Alzheimer's (Pick's disease, I think) in her early forties. Very sad for the whole family.

[CDHart]

That's OK -- Cindy's a prettier name, IMO, anyway. What I don't understand about Alzheimer's is that years ago, you never heard about it at all. And I don't think that those who were called "senile" were nearly as large a percentage of the population as Alzheimer's patients are. Unless it's just that I work here and see more of them.

Carolyn

[RonF]

Drilling down into the original press release reveals that the whole thing was funded by NIH. Patents will be forthcoming, probably owned by the University, once the whold system becomes better characterized.

[KC Burke]

.....I almost hate to do this...but not enough to avoid it....

Hey, Laz! There is hope for you yet!