Alzheimer's Research Target May Be a Dead End

Amyloid Plaques

Articles like this are two-edged swords. From OurAlzheimers.com:

Alzheimer's Research Target May Be a Dead End: By E.J. Mundell HealthDay Reporter Sunday, Jan. 27, 2008; 3:00 PM Copyright © 2008 ScoutNews, LLC. All rights reserved. SUNDAY, Jan. 27 (HealthDay News) -- A once-promising pathway for research into preventing and treating Alzheimer's disease may have been derailed by a surprise chemical finding, researchers report. Scientists in laboratories around the world have been investigating drug candidates called amyloid inhibitors, which many experts believed could keep proteins such as amyloid-beta from sticking together in brain tissue. This type of “sticky” protein plaque build-up is a hallmark of Alzheimer's disease. It also characterizes brain illnesses such as Huntington's disease and “mad cow” disease. But the new study, published Jan. 27 in the journal Nature Chemical Biology, may sound an unexpected death knell for amyloid inhibitor research. In the study, a team of chemists at the University of California, San Francisco, found that these candidate drugs form large, unwieldy clumps themselves, rendering them useless as targeted therapy against amyloid in the brain. [...snip...]

Basically, the thought was that Alzheimer's is brought on by proteins called amyloids that form large clumps within the brain called plaques. These plaques aggregate around nerve pathways and essentially clog down all functions. The plaques are very small and since are made of similar proteins as naturally found in the brain do not show up on MRIs and other imaging techniques. Various theories are bouncing around but the predominant one is that this is natural and that if we were to live long enough, eventually these plaques would affect all of us. Not a pleasant thought. Researchers are naturally asking the right questions. What if they came up with a chemical that locked up the amyloids before they could form plaques. “Amyloid inhibitor” research has been in the forefront on the war against Alzheimer's. While not a vaccine approach, a true working amyloid inhibitor could be taken on a regular basis after a patient hits, say, 40 or 50 years old. This would not prevent the root cause of Alzheimer's (amyloid production) but rather prevent the formation of plaques. No plaques, no Alzheimer's. There is a problem... The anti-amyloid chemicals stick together and clump. Think of each molecule as a long strip of scotch tape. And then the strips sticking together and eventually forming balls of tape, or in this case, balls of drug. Then, just as in the tape, the balls will stick to everything making them useless. To make matters worse, since they clump, they cannot even get through the membranes of the brain to reach the amyloids. This example shows a classical problem as one tries to scale a chemical experiment up from a beaker into a complex biological solution. Our bodies are extremely complex chemically and physiologically. To make matters worse, drugs need survive being introduced into the body. They must be able to either be ingested or injected, travel to the targeted areas, and only affect what we want them to. In most cases, this is not purely so. That is why drugs have side effects. They target more than just what we want them to. So, all is lost in this research area, right? Well, not for certain. The article does continue and say that several prominent researchers are saying that further pursuit in this area is a waste of time. They reason that the drug-clummping problem is just too fundamental to solve and that time and energy pursuing this avenue will take away from other solutions not yet studied in earnest. I have to personally question if the nay-sayers are really speaking from a “pure” sense of scientific reason or are they trying to get research $$$ in other avenues. Scientists crack me up, I know, I am one. However, they may be right. This is a very difficult problem. Clumping of biological-type molecules is common and very difficult to solve. To be effective:

• the drug must not clump
• must be stable on the shelf
• must survive injection or ingestion
• pass through the membrane
• be in high enough quantities to be stabilize large amounts of amyloid
• not clump to anything else
• then allow the captured amyloids to pass back out of the brain
• be ejected from the body or be destroyed elsewhere in the body (usually the liver)

Sounds daunting but is theoretically possible. The good news is that at least we know what we need to do if this should evolve into a treatment. Alzheimer's is quickly becoming one of the most researched diseases and with good cause. It is horrible. I know. I am watching my beloved mother-in-law disappear before our eyes and it breaks my heart. The effect on her and those around her (her husband of 50+ years, my wife and children, her friends and other relatives) is almost unspeakable. And with an overall aging population due to improvements in heart and cancer care and the Baby Boomers coming of age, this disease is set to cripple the population. Get moving, researchers.

[posted by Bobblehead]