Preamble

In July 2009, Dr. Knopman was quoted in the Minneapolis Star-Tribune as stating: "Despite years of research, drug companies have struggled to find an effective treatment. Part of the problem, Dr. Knopman of Mayo says, is timing: Symptoms only surface 20 to 30 years after patients develop the disease. By then, it's too late"

Current Alzheimer's Cause/Cure Theories

Beta-Amyloid Protein plaques: At the present time it appears that most of the research is directed towards the Beta-Amyloid Protein plaques found in the brains of Alzheimer’s victims. It is not currently known if the plaque found in the Alzheimer’s brain is the “cause of” or the “result of” Alzheimer’s. Some people have been found to have Beta-Amyloid plaques in their brains but did not show symptoms of Alzheimer’s. Also found in the Alzheimer’s brain are tangles of a protein called Tau. This Tau is also a suspect in the search for the cause of Alzheimer’s. 

AOL Health News 6/23/2008 reports findings of Dr. Ganesh M. Shankar and Dr. Dennis J. Selkoe of Harvard Medical School. “Researchers have caused Alzheimer’s symptoms in rats by injecting them with one particular form of Beta-Amyloid. ...other forms of Beta-Amyloid did not cause illness, which may explain why some people have Beta-Amyloid plaque in their brains but do not show disease symptoms.” 

          (1.)“Two-molecule form of soluble Beta-Amyloid produced characteristics of Alzheimer’s in the rats.

          (2.) There was no detectable effect from the (a.) insoluble plaque or the (b.) soluble one-molecule or (c.) soluble three molecule forms. The question is why one has the damaging effect and not others.” 

                       (Note: Four varieties of plaque are involved here.)

Vacination strategies for Azlheimer's disease remain an area of intense interest. But some critics have questioned whether amyloid-B vacination was simply a way to reverse cerebral amyloidosis without affecting other componetns of Azlheimer's disease....

We have learned a great deal about the possible pathogenic role that amyloid in its various forms might play in Alzheimer's disease pathogenesis, but the final demonstration that reversing amyloid pathology ameliorates the disease itself is still lacking."



AMDA "Caring for the Ages" April 2009 contains a guest editorial by Dr. Richard J. Caselli, MD. (Chair of Neurology at Mayo Clinic, Scottsdale, AZ and professor of neurology at Mayo Medical School, Rochester, MN) 

"There is widespread belief that amyloid neurotoxicity is at the heart of Alzheimer's disease pathogenesis, yet trials of very sophisticated and effective antiamyloid strategies have failed to halt, reverse, or even convincingly slow the disease in patients. These findings have caused some experts to reconsider whether we may have misunderstood amyloids's role in Alzheimer's pathogenesis. While we all are familiar with the pathologic hallmark of amyloid plaques, we may be less aware that neuronal disyfunction more likely reflects soluble amyloid oligomers, rather than insoluble plaques... 

Stem Cell Research and Therapy Potentials:

The Alzheimer's Association Newsletter for Summer 2009 discusses this exciting area of research and theory. "Stem Cell therapy has not only the potential to introduce cells into the brain to replace cells that have degenerated or died but also to introduce cells that can function as small factories to produce natural substances, such as powerful nerve growth factors, that the brain needs to protect itself and to regenerate damaged parts.". Until recently it was thought that the only means of introducing stems cells into the brain was to: (1.)  perform "Neurosurgery and implant the cells in the brain.  (This method  would be very expensive and also potentially dangerous because of the risk of injury to the brain in the implantation process or the causing of an infection in the brain.) (2.) Recently a method has been discovered that will permit stem cells to be non-invasively delivered to the brain using an intranasal delivery method developed by Dr. William H. Frey, Director of the Alzheimer's Research Center at Regions Hospital in St. Paul, MN. (While this method would suggest great future potential, obviously much more research and testing will be necessary and required before this method and treatment is ready for the FDA approval process.) 

 
Detection using Functional Magnetic Resonance Imaging - fMRI:

Time Magazine for Wednesday 26 August 2009 contained an article by Alice Park on work now being conducted by researchers at Cleveland Clinic into a new method of early detection of Alzheimer's. "What Britney Spears Can Reveal About Alzheimer's"

The article says "they may have found a way to identify those most at risk of developing the neurological disorder long before symptoms develop - simply by asking them whether they recognize celebrities such as Britney Spears and Johnny Carson. It turns out that when people who are at highest risk of Alzheimer's try to recognize a famous name, their brains activate in very different ways from those of people who aren't at risk...scientists can actually see this difference using functional magnetic resonance imaging, or fMRI."

The research was reported in the journal "Neurology".  "team led by Stephen Rao, a brain imaging specialist...study of 69 healthy men and women aged 65 to 85...Rao's team found that when volunteers saw names such as Britney Spears, George Clooney, Albert Einstein and Marilyn Monroe, those who were at the highest risk of developing Alzheimer's - those with the genetic makeup (Version of gene for a protein called apolipoprotein E4..(ApoE4) and a family history - showed high levels of activity in the hippocampus, posterior cingulate and regions of the frontal cortex, all areas involved in memory. The control group showed the opposite pattern. Their brains became more excited when they saw unfamiliar names, which included Irma Jacoby, Joyce O'Neil and Virginia Warfield....This could mean that the at risk people were working harder to recognize the well known celebrities, compensating for already damaged or destroyed neurons that were no longer functioning, while the control group had to struggle only when trying to place the names of noncelebrities."

 "The idea is not necessarily to diagnose Alzheimer's earlier, says Rao. But imaging studies can help to identify those most vulnerable to cognitive decline so they can participate in clinical trials of new drugs designed to postpone or reduce symptoms."

 Note: I doubt very much that clinical trials will ever be based on pools of individuals that have been detected through the large numbers of testing needed for such a selection process...At the present time there are no drugs available to postpone or effectively reduce symptoms. Would the average person care to know this information if at the same time nothing can be done but worry...The early part of the article stated: "the disease has already been ravaging the brain for a decade or more, causing irreversible damage...However, .according to Knopman of the Mayo Alzheimer's research department, it is far longer than a decade...(He talks of 2-3 decades.)  In July 2009, Dr. Knopman was quoted in the Minneapolis Star-Tribune as stating: "Despite years of research, drug companies have struggled to find an effective treatment. Part of the problem, Dr. Knopman says, is timing: Symptoms only surface 20 to 30 years after patients develop the disease. By then, it's too late"  This is certainly an interesting development but does it have practical value. We need more attention to finding a cure and less to early detection.

 
SEE:  Article this section "A New Direction for Alzheimer's Research" that discusses brain cells called GLIA or click on this link:

          "A New Direction for Alzheimer's Research"

Current Clinical Trials

(1.)  The Wall Street Journal, June 18^th, 2008 reports on some of the leading amyloid therapy programs for Alzheimer’s disease presently involved in clinical trials. “Drug companies have focused on the amyloid hypothesis because a considerable body of research suggest that the brains of “Alzheimer’s patients contain large amounts of certain types of amyloid. But in the relatively few studies in which amyloid has been removed from mice’s brains, cognitive symptoms haven’t necessarily improved. And human autopsies show that the mere presence of large amount of amyloid doesn’t always correlate with the presence of Alzheimer’s, according to Bruce Miller, clinical director of the University of California at San Francisco Memory and Aging Center.” 

Elan/Wyeth is sponsoring clinical trials with their drug “Bapineuzumab” and are currently in Phase III of the trials. (Phase II results show trend toward improvement of cognitive symptoms.     

          Note (1.) : The International Conference on Alzheimer's, in Chicago, July 2008.  "Elan Corp. and Wyeth said complete data from the midstage trial of their experiental drug...supports their prior decision to move the drutg into more advanced studies before a thorough assessment could be made....full findings on the drug...remain inconclusive...their study  indicated that bapineuzumab had shown some effectiveness in cleansing the brains of amyloid....Still the 234 patients on the whole showed no improvement in demential symptoms. The companmies tjhen opted to proceed with a costly late-stage trial-a move that drew questions from inside and outside the scientific commiunity." 

          Note (2.) :  The Wall Street Journal July 3-5, 2009 reports: "Bapineuzumab, which is one of the most advanced treatments in developement, had mixed results in earlier trials and is considered a high risk investment. The so-called therapeutic vaccine aims to fight the progression of Alzheimer's by using anti-bodies to remove amyloid. "I have become more skeptical about Bapineuzumab than I was, say, two years ago or three years ago, partly because we've learned a lot more about the dynamics, if you will, of amyloid in the brain," said P. Murali Doraiswamy, professor of biological psychiatry at Duke University Medical Center. Amyloid appears to turn over rapidly in the brain, so a treatment that clears it from the system might have only a temporary response, requiring additional or more frequent treatments, he said.  There also have been cases of brain swelling in some Bapineuzumab-trial participants, prompting trhe companies to stop giving some patients in late stage trials, the highest of three dose levels of Bapineuzumab."

Eli Lilly is sponsoring clinical trials with their drug “LY450139.” They are currently in phase III of the trials. Phase I study lowered amyloid in some but not all regions of the brain. 

Myriad is sponsoring clinical trials with their drug “Flurizan’. They are currently in phase III

          Note: The Wall Street Journal for July 3-5, 2009 reports that: "Two late stage trials of experimental treatments, Myriad Genetics Inc.'s  Flurizan and Neurochem Inc.'s Alzhemed, have failed in the last two years..               

Pfizer sponsored clinical trials with their drug “Lipitor”. No effect on cognition in trial.  

Pfizer - New trials underway (9/4/2008) on drug  latrepirdine (Dimebon) being co-developed with Medivation Inc. Dimebon, orignally used as an antihistamine in Russia (25 years ago) and no longer on the market. "Whether Dimebon truly slows down the disease or is just a better treatment for symptoms than are currently available medications remains to be seen.) Currently in phase three study. . 

       Update: 3/3/2010 - The Alzheimer drug latrepirdine (Dimebon) did not meet either of its primary research targets in a late-stage clinical study, (Phase III clinical trial results) faring no better than a placebo at treating the disease, according to Pfizer Inc., the drug's manufacturer.

          Note: The Wall Street Journal 7/13/2009 in an article: "New Alzheimer's Gene is Pinpointed" references Dimebon. "The TOMM40 gene is related to how easily molecules can get into and out of the surface of the mitochondria, the energy center of cells. Some researchers propose that this permeability is part of Azlheimer's disease, according to Dr. Thies. One experiment al drug called Dimebon, which is being studied by Medivation Inc. and its partner Pfizer Inc., may be a therapy that acts throught that mechanism, Dr. Thies said."  Note: See above Dimebon update 3/3/2010.               

Prana Biotech is sponsoring clinical trials with their drug “PBT2”. They are  in phase II.                     

(2.)  Minneapolis Star-Tribune 7/30/2008 (Associated Press) reports "Experimental Alzheimer's Drug has the field of research excited." The drug was developed by Singapore-based Tau-RxTherapeutics." The drug called Rember." "experimental drug shows promise for halting the progression...by..breaking up the protein tangles that clog victims' brains...Even if bigger, more rigorous studies show it works, Rember is still several years away from being available, and experts warned against over exuberance. But they were excited...The drug is in the second of three states of developement...The main chemical in Rember is available now in a different formulation in a prescription drug sometimes used since the 1930s for chronic bladder infections - methylene blue. However, it predates the federal Food and Drug Administration and was never fully studied for safety and effectiveness, and not in the form used in the Azheimer's study, TauRx's chief, Claude Wischik and other doctors cautioned." 

Detail Trial Notes on Rember:The group conducted a randomized double-blind
trial in 321 people with mild to moderate Alzheimer's. Participants
received 30, 60, or 100 mg of Rember or a placebo three times a day.
After 24 weeks, people with moderate Alzheimer's who took 60 mg of the
drug showed significantly less cognitive decline than those on the
placebo. This advantage was sustained when the trial was extended to
50 and 84 weeks. Although these results are promising, Rember's apparent benefits must
be confirmed in appropriately designed, larger trials. A number of
other compounds that have had similarly promising results have not
proven to be effective when well-designed trials were carried out.
 

(3.) Minneapolis Star-Tribune 7/13/2009 reports "Could Alzheimer's Drug be on Horizon?" reports on a study described at the International Alzhiemer's Conference in Vienna this month. "Humanetics Corp, though thinks it's getting close. The Eden Prairie based drug company, in collaboration with the Mt. Sinai School of Medicine in New York, recently released a study that suggests a natural anti-diabetic compound, dubbed NIC5-15, can help safely reduce dementia in Alzheimer's patients...Clinical studies show that NIC5-15 interferes with gamma-secretase, an enzyme that turns Beta-amyloid protein into plaque that clogs and eventually kills nerves cells, ... More important, NIC5-15 didn't interfere with a gene that controls white blood cells and the immune system..."

     Note: This is one of the many approaches that target the Beta-Amyloid protein plaque's...The same article later notes: "In recent years, however, some researchers have questioned whether Beta-amyloid plaque even leads to Alzheimer's. The brain is such a complicated system that it's hard to pin down one primary cause ofr the disease, Dr. Knopman of Mayo said."

(4.) Caring for the Ages, (AMDA Journal) October 2009 has a dreary report under the title "Failed Drug Trials Suggest Alzheimer's Shift." An article by Michele G. Sullivan reported the bad news. "Vienna - Alzheimer's drug researchers served up a string of bad news at the International Conference on Azlheimer's Disease, presenting one failed trial after another...None of these strategies tested - such as blocking amyloid, improving insulin sensittivity in the brain, or even doubling  up on agents that improve synaptic signaling - was able to alter the steady rate of cognitive and functional decline in patients with mild to moderate Azlheimer's...No effect seen with Rosiglitazone...end of the road for Tarenflurbil...combo no better than one...Divalporoex treatment over 2 years didn't delay onset of agitation or psychosis in patients with Alzheimer's disease , and patents taking the anticonvulsant showed significantly more brain volume loss on MRI at year 1 than did those taking placebo."

Note: "Phase I studies are early-stage human clinical trials, Phase II are midstage and Phase III are late stage trials designed to demonstrate treatment efficacy."

  Last Update: 3/3/2010