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In Search of an Alzheimer’s Cure
Posted By admin On March 27, 2007 @ 11:00 am In Articles,Drugs and Treatment | No Comments
March 27, 2007
A cure for Alzheimer's disease remains a holy grail for a growing number of scientists and medical researchers around the globe, including those funded by The Fisher Center for Alzheimer's Research Foundation. With 4.5 million Americans currently suffering from Alzheimer's, and that number expected to triple in the coming decades, an effective treatment is needed more than ever. While existing Alzheimer's drugs offer limited benefits, exciting new drugs in the testing pipeline offer tantalizing hope for major progress for millions of Alzheimer's sufferers worldwide.
Currently, drugs known as cholinesterase inhibitors that are prescribed for Alzheimer's disease may slow progression of the disease during its early stages. However, they do not stop the eventual worsening of the disease. In addition, they do not work on everyone. To date, only five drugs have been approved to treat Alzheimer's. The last one to be approved, memantine, for moderate to severe disease, was in 2004.
New drugs that target the underlying mechanisms of the Alzheimer's disease process are currently undergoing testing in medical centers and laboratories worldwide. These medicines are called "disease-modifying drugs" because, in theory at least, such drugs might stop or even reverse the mental decline that occurs with Alzheimer's. They might even prevent memory problems from taking hold in the first place.
The drug testing process, however, can be frustratingly slow. Drugs are first investigated in laboratories and in animals. If a compound shows promise, it may be tested in people. This involves three stages of testing. The first, called Phase 1, tests the drug in small groups of people to ascertain safety. If it passes Phase 1, it goes on to Phase 2, which tests the drug in small groups of people both for safety and some measure of effectiveness. If the drug passes Phase 2 it goes on to Phase 3. These are large-scale trials involving hundreds of people. Phase 3 trials test the drug for continued safety and effectiveness.
Fewer than one in five experimental drugs that enter the clinical trials pipeline prove effective and safe enough to ultimately be approved by the Food and Drug Administration. Understandably, it may take many years of study and testing before a new drug becomes available for sale at your corner pharmacy. Even after a drug is approved, follow-up studies are continued to monitor long-term safety.
Promising Experimental Treatments
Several potential, disease-modifying drugs are currently undergoing testing. For example, Phase 3 trials were recently completed for a new drug, called Alzhemed, that may slow the course of Alzheimer's disease. It is supposed to lower the formation of clumps, or aggregates, of beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer's. In a few months, results of that study, which involved more than 1,000 men and women with mild to moderate Alzheimer's disease, should become available. If the drug does prove to be safe and effective, it could prove a potent new weapon in the battle against Alzheimer's.
Another drug, called Flurizan (from Myriad Genetics), is also in late-stage trials to see if it helps slow, or reverse, the course of disease. Results of those studies, however, will likely not be available for at least a year. Other scientists are looking at Valproate, an epilepsy drug that may offer benefits for those with Alzheimer's. And, research is ongoing on huperzine A, a natural substance derived from a Chinese moss, that may have memory-boosting properties.
Other companies are testing vaccines that generate antibodies against beta-amyloid. While early vaccine trials in people looked promising, some people with Alzheimer's who received the vaccine developed encephalitis, a life-threatening inflammation of the brain. Intriguingly, however, some who got the vaccine did develop antibodies against beta-amyloid and may have experienced delayed progression of their symptoms. Drug companies are looking into safer alternative vaccines that prod the immune system into clearing the brain of beta-amyloid plaques.
Dozens more drugs are in development. A total of nine are in Phase 3 testing. Someday, these promising new drugs may prove useful for those with Alzheimer's disease. They may be mixed with existing Alzheimer's medications, similar to the drug cocktails currently prescribed for people with AIDS. Some of these disease-modifying drugs may also prove useful for those with mild cognitive impairment, a less severe form of age-related memory and cognitive loss that sometimes progresses to Alzheimer's disease. Drugs may eventually be given to healthy, mentally sharp individuals to prevent Alzheimer's or memory loss from ever taking hold at all.
The Fisher Center for Alzheimer's Research Foundation continues to fund groundbreaking research into the underlying causes of Alzheimer's in the quest for a cure. Scientists at The Rockefeller University and other research institutes worldwide are continuing critical basic research into what happens in the brains of those with Alzheimer's disease, and how the relentless downward progression of disease might be halted, or reversed.
In the past year, scientists at the Fisher Center for Alzheimer's Research at The Rockefeller University in New York City have published scientific reports that may one day lead to an effective cure for Alzheimer's disease. In one, Fisher Center scientists found that a protein in the brain, called WAVE-1, is critical to the communication and connections between brain cells, a vital process in thinking and memory.
"One of the key features of Alzheimer's is the devastating loss of memory and other mental skills, caused primarily by the loss or malfunction of connections between brain cells," says Paul Greengard, Ph.D., the Center's Director and recipient of the Nobel Prize in Physiology or Medicine in 2000. "By being able to control the growth of new brain cell connections, or stopping the loss of old connections, doctors may one day be able to prevent or reverse dementia."
In another study, Fisher Center researchers discovered that a brain protein called p11 plays a key role in regulating how much of the mood-elevating chemical serotonin remains active in the brain. The finding may one day lead to novel therapies to treat depression, a major mental illness that afflicts some one in ten American adults each year, including many with Alzheimer's disease.
Most recently, Rockefeller scientists identified a potential therapeutic target, called casein kinase 1, which is an important signaling protein. Chemicals that block this protein were shown to reduce beta-amyloid levels in cultured cells. If this were to occur in the brain, it might stop the progression Alzheimer's or alleviate some of its symptoms.
For more information on these and other exciting avenues of research, or to make a donation to end Alzheimer's disease, visit The Fisher Center for Alzheimer's Research Foundation at www.ALZinfo.org .
Yong Kim, Jee Young Sung, Ilaria Ceglia, et al: "Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology" (letters). Nature, Volume 442, 17 August 2006/doi:10.1038/nature04976.
Per Svenningsson, Karima Chergui, Ilan Rachleff, Marc Flajolet, Xiaoqun Zhang, Malika El Yacoubi, Jean-Marie Vaugeois, George G. Nomikos, Paul Greengard: "Alternation in %-HT1B Receptor Function by p11 in Depression-Like States." Science, Volume 311, 6 January 2006, pp. 77 -- 80.
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