These drugs are used primarily to ease symptoms of cognitive loss. In general, improvements are modest. Current medications for Alzheimer’s may slow mental decline for a limited time during the early stages of the disease, but do not stop the eventual downward spiral. Others drugs, such as anti-depressants and anti-psychotics, may be prescribed to ease agitation and aggressive behaviors.
However, the need for an effective treatment to halt or even reverse the memory loss of Alzheimer’s is as urgent as ever. So is the need to prevent the disease from taking hold in the first place. The number of cases of Alzheimer’s is expected to triple by the end of this century, as the U.S. population ages, causing proportionally more people to be in their 70s and 80s, when an Alzheimer’s diagnosis grows more likely.
A number of experimental drugs and vaccines are in late-stage testing to determine whether they can halt, reverse, or prevent the onset of Alzheimer’s. Unlike existing treatments, these medicines may actually modify the course of the disease. We asked Dr. Paul Greengard, Nobel laureate and medical director of the Fisher Center for Alzheimer’s Disease Research, to comment on new treatments in the Alzheimer’s pipeline. The work of his lab at The Rockefeller University has contributed to an understanding of what goes wrong in the brain in Alzheimer’s disease, as investigators around the globe continue their search to find a cure for an ailment that affects 25 million people worldwide.
PYM: Dr. Greengard, is the attempt to reduce beta-amyloid the most promising approach to developing new, more effective treatments for Alzheimer’s disease?
Dr. Greengard: A majority of scientists involved in Alzheimer’s research believe that beta-amyloid is the main pathogenic factor responsible for the degenerative changes that occur in the brain during Alzheimer’s disease. Thus, drugs that lower beta-amyloid levels in the brain are expected to offer the most promising treatments. However, Alzheimer’s is a complex disease. Treatments that do not target beta-amyloid might also be beneficial and might ultimately be used in combination with anti-amyloid therapies.
PYM: When might an Alzheimer’s treatment that stops the disease from getting worse become available? Would it help patients who already have Alzheimer’s disease?
Dr. Greengard: A drug designed to slow progression of Alzheimer’s disease, Flurizan (tarenflurbil), has recently completed late-stage testing on large numbers of patients, and the results of those tests are anxiously awaited. Smaller scale clinical trials of Flurizan carried out over the last few years have shown promise. In those trials, the drug appeared to slow progression of the disease in many patients, but only the results of the larger trials will be conclusive. Flurizan reduces formation of a particularly toxic form of beta-amyloid, called beta-amyloid 42. In the next few years, additional drugs that lower either beta-amyloid 42 or total beta-amyloid will have been tested in large clinical trials.
We believe that an effective Alzheimer’s therapy will involve reducing levels of beta-amyloid. However, it is not known whether patients who already have Alzheimer’s could improve substantially if the progression of the disease is slowed or even stopped. Most likely, those who will benefit most from beta-amyloid-lowering drugs will be people in the earliest stages of disease, for whom extensive brain damage has not yet occurred.
PYM: Dr. Greengard, are vaccines that clear beta-amyloid from the brain a promising approach to treating, and perhaps even curing, Alzheimer’s disease?
Dr. Greengard: Vaccines that are designed to clear beta-amyloid are a very exciting line of research. They can be divided into two classes, “active vaccines” and “passive vaccines.” The active vaccines consist of a form of beta-amyloid that is injected into the body. This causes the immune system to produce antibodies that attach to beta-amyloid, causing it to be cleared from the body. An “active” vaccine was tested in patients a few years ago. Unfortunately, the tests had to be stopped because the vaccine caused a small number of patients to experience swelling of the brain. This may have occurred because the vaccine also stimulated the immune system to produce specialized T-cells. Drug companies are working on beta-amyloid vaccines that are designed not to stimulate specialized T-cells, in the hope that side effects such as brain swelling and inflammation can be eliminated.
"Active" and "passive" vaccines are now being tested in the treatment of Alzheimer's disease.
“Passive” vaccines consist of antibodies made in the laboratory that are injected into a patient. The antibodies target beta-amyloid. The vaccine is called “passive” because when it is injected into the body it does not stimulate the patient’s immune system to attack beta-amyloid by producing its own antibodies or T-cells. As a result, passive vaccines are not expected to produce the toxic effects that were caused by the first, active vaccine tested a few years ago. Passive vaccines are also a very promising approach. A passive beta-amyloid vaccine is currently being tested in Alzheimer’s patients in clinical trials that will take several years to complete.
PYM: Doctors often recommend a daily aspirin, which has anti-inflammatory and blood-thinning properties, for people at risk for heart disease. Is taking a non-steroidal anti-inflammatory drug (NSAID) like aspirin each day a good idea for someone with Alzheimer’s or at risk for the disease?
Dr. Greengard: Current anti-inflammatory drugs have not been shown to be useful for treating Alzheimer’s disease. There is evidence, however, that long-term use (about 5 years) of some but not all NSAIDs (e.g., ibuprofen but not celecoxib) might lower the risk of developing Alzheimer’s disease. However, these drugs can have dangerous side effects, such as gastrointestinal bleeding and ulcers for some people. Nevertheless, there is a lot of evidence that inflammation plays an important role in Alzheimer’s disease. It is hoped, as our basic knowledge of inflammation and its role in the brain grows, that anti-inflammatory drugs can be developed to treat or prevent Alzheimer’s disease.
PYM: Do natural remedies (e.g., Omega-3 fatty acids, ginkgo biloba, curry) hold promise for the prevention of Alzheimer’s disease?
Dr. Greengard: The evidence here is conflicting. For example, there is evidence that DHA or other omega-3 fatty acids may help reduce the risk of Alzheimer’s. Some evidence suggests that curcumin (a derivative of the Indian curry spice turmeric) may also reduce Alzheimer’s risk. Most of this evidence is derived from retrospective studies and are based on correlations. These are not the most reliable kinds of studies. Instead, well-controlled tests on large groups of people need to be carried out first to assess the value of these substances. In fact, a large well-controlled clinical trial that tested the ability of ginkgo biloba to reduce the risk of Alzheimer’s has recently been completed. The results of that trial could be announced in the next several weeks.
About Dr. Paul Greengard, Director of the Fisher Center for Alzheimer’s Disease Research at The Rockefeller University:
Dr. Paul Greengard was awarded the year 2000 Nobel Prize in Physiology or Medicine for his pioneering work in delineating how neurons communicate with one another in the brain. During a half-century of research, he has been lauded for his singular contribution to our understanding of the complex signaling processes that occur within each of the 100 billion or more nerve cells in the human brain. He is the Vincent Astor Professor at The Rockefeller University and Director of the Fisher Center laboratory. Dr. Greengard is also a member of the National Academy of Sciences and has received more than 50 awards and honors throughout his career. He is the author of nearly 1,000 scientific publications.
For more information, please visit: www.ALZinfo.org. For up-to-date information on clinical trials currently underway, please visit: www.clinicaltrials.gov.
Source: www.ALZinfo.org. Preserving Your Memory: The Magazine of Health and Hope;
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