I saw a clinical trial for a Bristol Myers Squibb drug candidate in MCI, so I was resarching the present state of amyloid reduction research - not encouraging. One drug worked - it cleared plaques, but gave no cognitive improvement to AD patients (The FDA is actually requiring symptom improvement - imagine that!). Another drug trial was terminated in phase III becuase patients actually got worse :(
I ran across this and thought it was interesting enough to share: http://blogs.forbes.com/robertlangreth/2010/08/23/renegade-researcher-says-alzheimers-drugs-from-bristol-myers-pfizer-may-be-unsafe-or-ineffective/
I read an article yesterday that said the amyoid plaque does not cause AD and the drugs trials that are testing a drug to remove it are failing. It sounds like the same article.
Yep, the latest studies seem to hint at the possibility that amyloid plaques are symptomatic of the underlying inflammation, but it's the latter that destroys cognition. The plaques are more like pearls made by oysters to protect themselves from the irritant. So, the focus seems to be: what is triggering the inflammatory process, and how can we prevent it?
I think a big clue that amyloid plaques are a symptom is that study of all the nuns brains and brains of other people who had no symptoms. The plaque is really not an indicator of definite AD and in time I believe that will show to be true. As said above 'it is more like pearls' not the cause of cognitive loss.
Here's a very comprehensive article for those interested: http://pubs.acs.org/cen/coverstory/88/8814cover.html
These articles are so clinical, but when stop to think as you read, of all of the lives - spouses, children, siblings ,etc. - that are affected with each drug trial that tests the latest hypothesis, the glimmer of hope in a hopeless situation, it's heartbreaking - sigh.....
"A new Alzheimer's compound kept toxic clumps from forming in the brains of mice, without causing side effects seen in similar drugs, U.S. researchers said on Wednesday....One chemical, compound 4, kept brain plaques from forming, but left other brain processes alone. The results were so promising at reducing levels of the protein that a private San Diego-based company called Neurogenetic Pharmaceuticals Inc has licensed the patent. The company has dubbed it NGP 555..."
"They tested the drug on mice that were genetically designed to develop large amounts of beta amyloid in their brains. One group of rodents ate food laced with NGP555 every day for seven months while another group received no medication.
The researchers examined the brains of the mice at the end of the test. The animals that received the drug showed no signs of plaque development while the others had large amounts of beta amyloid.
The scientists didn’t test the mental abilities of the mice, so they don’t yet known whether the drug prevents Alzheimer’s symptoms in the animals."
Why wouldn't they test the mental abilitites of the mice, expecially since we now know that clearing plaques doesn't improve symptoms, and can even make them worse? I think the FDA should tell all these researchers - if you can't IMPROVE SYMPTOMS in mice, forget about it, there is no point in moving into human trials.
A new target for Alzheimer's emerges: Exciting discovery generates a new path for treatments: http://www.examiner.com/health-news-in-boston/a-new-target-for-alzheimer-s-emerges-exciting-discovery-generates-a-new-path-for-treatments
Frankly, after you've read enough of these articles none of them are "exciting," but interesting in this one was the stat on trial drugs: "A search of ClinicalTrials.gov reveals 712 ongoing clinical trials to treat Alzheimers disease with drugs. 346 of them are in Phase 2 or Phase 3 clinical trials, meaning they have advanced past the initial safety testing in people, and are now in trials to examine their effect on memory and cognitive thinking in Alzheimer’s patients. This adds up to billions and billions of dollars now being spend each year on the tiny hope that one of these drugs may be able to slow down the irreversible dementia that characterizes this horrific disease."
This about sums up the Amyloid research: "Never has the neuro area embraced a mechanism so early and fervently, with so little to show for it."
Also form this article (Alzheimer's Therapeutics Reviewed by NeuroInvestment: http://www.marketwire.com/press-release/Alzheimers-Therapeutics-Reviewed-by-NeuroInvestment-TSX-NPC-1312891.htm ): "A recalibration of what constitutes a comprehensive AD pipeline is required, which opens the door for therapeutics utilizing other mechanisms, such as those addressing tau, metal-binding, and neurotrophin-enhancement.
The goal of AD treatment may also warrant a reset, as sustaining function farther into the lifespan may be as useful, and more safely viable, than is the elusive goal of disease-modification. Programs which sustain functional autonomy more effectively could emerge from a host of cognitive enhancement targets; including nicotinic and/or muscarinic receptors, 5HT-6, and/or H3 antagonism.
Over 180 therapeutics programs from 110 companies are included in this review. They range from the failed or failing leviathan programs, like JNJ/Pfizer/Elan's bapineuzumab, Lilly's semagacestat, and Pfizer/Medivation's Dimebon; to those with early clinical data, such as Allon Therapeutics (TSX: NPC), Targacept (NASDAQ: TRGT), Ceregene, EnVivo Pharmaceuticals, and Prana's PBT-2; to still under-the-radar programs from such companies as Axerion, Cortex Pharmaceuticals (NYSE Amex: COR), AgeneBio, NsGene, and Synosia Therapeutics.
The September issue also considers the nascent area of Alzheimer's biomarkers, and their lack of readiness for clinical 'prime time;' the dim prospects for redundant therapeutics from Vanda Pharmaceuticals, Somaxon, and Jazz Pharmaceuticals; and the controversial expansion of CNS drug development partnering by Cypress Biosciences (NASDAQ: CYPB). A review of the Danish neurotrophic specialist firm, NsGene, is also included."
Joan's breaking news link is interesting - New Findings Contradict Dominant Theory In Alzheimer's Disease http://www.bioresearchonline.com/article.mvc/New-Findings-Contradict-Dominant-Theory-0001
This research indicates that it is the cells' inability to secrete the beta amyloid that causes the neurodegeneration. I imagine there are a lot of researchers (the ones invested in clearing beta amyloid) with stomachs that are turning tonight. I hope they are quick to switch gears...
We went through the entire Bapineuzinmab (sorry about the spelling) trial. I was certain my wife was getting the drug. After all the mental tests, blood draws, waiting, travelling, constant imersion into the reality if Alz. I wonder why we did it. Just now I remembered. I felt at the time I was proving to her family that I was doing everything I could. What a waste of time that part of the effort was. Sorry to sound so cynical, you understand.
Well, I think everyone who participates in clinical studies earns karma points. Maybe the ones we were in didn't amount to anything, but they paved the road up until this point.
I saw one video of a scientific lecture that explained it all.
To do experiments you need an "animal model" to experiment with. We have rats that grow human cancers and develop heart & lung disease etc. Scientist then try out different drugs to cure the mice.
There is a 'engineered' mouse/rat available to researchers that grows amyloid plaques. There IS NO mouse that develops the Tau tangles(!) Which is why so little research is known about them.
So, imagine yourself as a researcher who's paycheck depends on experimenting on something. You HAVE TO keep attacking the plaques (with no proof they are really the problem) or work elsewhere.
I really wanted to get my wife into testing. We went to 4 major AD centers in the LA Area. Within 6 months she was FIRST rejected twice for having symptoms that were "too advanced" and at the next two interviews they said her symptoms were TOO MILD(!) How can that happen? All this for the SAME STUDY!!! (you can search them on line) So I gave up.
My hb had no interest in them. He did not want to have to keep going through the MMSE test every time he went in. His neurologist never sounded like she thought any were worth it. This last visit was the first time she had mention doing them but I think it mainly might have been to do the genetic testing. I handed her his family history of AD and that is when she brought them up.