Newsletter
Research Advances of 2000 for Alzheimer's
The Alzheimer's Association has released the top research advances for 2000. In the two decades since Alzheimer's disease research began, understanding is increasing and the pace of discovery accelerating. There are many lines of research underway which will hopefully help to unravel the mysteries of this devastating and complex disease.
More is being learned about the causes of the disease and exploration of many promising therapies for its prevention is getting closer. Breakthrough studies are being published almost weekly.
Listed here is a brief summary of the research advances for 2000.
Diagnosis
Since there is no one laboratory disgnostic test for the disease current methods combine physical and neuropsychological testing and physician's judgement. This system has proven to be about 90 percent accurate.
One experimental study is focusing on brain imagin techniques to see if the early cognitive markers - changes in mental abilities and personality - can be linked to early biological changes in the brain. These brain imaging and scanning techniques are getting closer to pinpointing brain abnormalities that might enable physicians to diagnose people with Alzheimer's before symptoms appear.
Drugs - Existing and in Development
There is great hope that one day we can delay, and someday prevent the onset of Alzheimer's disease. The FDA recently approved the drug rivasttiggmine (Exelon®).
This drug along with two others, donepezil (Aricept®) and tacrine (Cognex®) treat symptoms by improving cognitive function. The FDA is reviewing other drug, galantamine (Reminyl®). As many as 60 new drugs designed to prevent or slow the progression of the disease are in various stages of development at this time.
Investigation of anti-inflammation drugs that will reduce the inflammation that accompanies plaque formation continues. Ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDS), appear to reduce the risk of Alzheimer's. Critical trials have been launched to determine whether treatment with certain NSAIDS will slow cognitive and clinical decline in people with Alzheimer's.
Scientists are also investigating certain cholesterol-lowering medications. Two studies published have shown that there is a relationship between certain cholesterol-lowering medications (statins) and decreased occurrence of Alzheimer's. Researchers at Boston University School of Medicine found that individuals who were prescribed certain cholesterol-lowering medications were about 70 percent less likely to have a dementia compared to people who had no diagnosis of high cholesterol or exposure to other cholesterol-lowering medications. While these two studies show a relationship between these medications and decreased occurrences, it does not prove cause. The Alzheimer's Association believes that appropriate clinical trials using statins as a potential preventive for Alzheimer's should be conducted.
Enzymes
Over the past ten years or more researchers have been looking for enzymes that might be central to the formation of beta amyloid - tiny protein fragments - that accumulate in the brains of people with Alzheimer's. Scientists believe that this plaque causes cell death which leads to the decline in the person's cognitive functions. A recently published study suggested that a subset of the enzyme beta secretase had been identified. Research suggests that by inhibiting the action of beta secretase, it may also be possible to inhibit the development of beta amyloid, preventing plaques from forming in the brain and thus preventing the progression of the disease.
Another study says that by inhibiting another enzyme - gamma secretase, it may also be possible to inhibit the development of amyloid plaques, consequently preventing the progression of Alzheimer's.
Clinical trials will be needed on both of these studies before it is known for sure whether inhibiting these enzymes will affect the disease.
Nerve Growth Factor
Research over the past several years has opened many doors that could lead to effective treatments for the Alzheimer's disease. The nerve growth factors (an essential chemical in the brain) approach is one of the many.
How it works is not completely understood but it is known to be one of several growth factors, or neurotrophic factors in the brain. While nerve cells in the brain do not divide in sufficient quantities to overcome Alzheimer's disease, they can repair themselves after injury, and neurotrophic factors promote this regeneration.
A study done at the University of California, San Diego on a gene therapy technique involving nerve growth factor, suggested that they were able to revive or restore brain cells in aging monkeys. The researchers took skins cells from older monkeys and inserted a gene that makes human nerve growth factor. They injected the modified cells into the brains of four monkeys. Once in the monkeys' brains, the modified cells began making nerve growth factor and appeared to revive brain cells.
The Food and Drug Administration has approved a Phase I clinical trial of the gene therapy experiment in humans. This is a step closer to determine whether this technique will affect the course of Alzheimer's disease.
Vaccine
In 1999, scientists at Elan Corporation genetically engineered mice that would accumulate amyloid in their brains. They then immunized them with a synthetic protein fragment called AN-1792 and found that is significantly reduced existing plaque and prevented further plaque from developing.
If this study can be replicated in humans, it would enable scientists to test amyloid reduction as a possible treatment. It is difficult for scientists to predict whether AN-1792 will be effective in humans since the immune system of a mouse is very different from a human.
Phase I safety trials on AN-1792 in other anumals and initiated multidose Phase I clinical trials in humans are underway and the initial results were announced at the World Alzheimer's Congress 2000. They showed that the potential vaccine was well tolerated in humans.
This test as well as another one being conducted at Harvard Brigham and Women's Hospital are very encouraging in the study for prevention, and possible treatment, of Alzheimer's disease.
Conclusion
There were other advances announced at the World Alzheimer's Congress 2000. This conferenc was held over a 10-day span in July and was attended by more than 5,000 world leaders in Alzheimer research and caregivers. It marked the first time these Alzheimer specialists have come together. This conference and the ongoing studies and research being conducted will unite the world in an effort to find a cure and treatment for this devastating disease.
As many as 4 million Americans suffer from the Alzheimer's disease. In April of 2001 a study was released that showed by the year 2010 the Medicare costs for people with Alzheimer's will jump by 54%. Between 2010 and 2050, the number of people with Alzheimer's will increase from an estimated 5.5 million up to 14 million, as the baby boomers enter the age of highest risk. This epidemic of Alzheimer's disease threatens to bankrupt Medicare and Medicaid if a cure and/or reasonable treatment for the disease is not found.
Other Alzheimer's research
As mentioned earlier, there are many and various approaches being taken while looking for a cure for Alzheimer's disease. No one can know for sure which is the right one, but we know that eventually a cure will be found if the researchers keep working. We are also very aware that for the research to keep going forward, the money must keep coming in.
Playing games
Research by Dr. Robert Friedland, Associate Professor of Neurology, Psychiatry and Radiology at Case Western University, Cleveland shows that the type of relaxation activities a person does durig the maturing years (20-60) can reduce the risk of developing Alzheimer's disease. Even after data was adjusted to take into account differences such as age, income, sex and education, the healthy subjects were more active between the ages of 40-60 than the patients with Alzheimer's. Alzheimer's disease patients are less active and more likely to decrease participation in intellectual activities during midlife. Less active people in leisure time were three to four times more likely to have Alzheimer's than people who are more mentally active.
The theory is that by performing more complicated mental tasks on a daily basis (i.e., crossword puzzles, board games, etc.) you build neural networks in the brain. Alzheimer's destroys those networks and people who have more connections will function for a longer period of time; in a sense, delaying the impact of the disease. It is difficult to conclude from this research whether mental activities helped delay the disease or whether the inactivities of the Alzheimer person was due to early, undetected signs of the disease.
Dr. Friedland's study also found that it is never too late to start in intellectual pursuits. He is critical of some nursing homes because they do not supply more mental activities for their residents, but just turn on the television. Activities such as crossword puzzles, playing musical instruments, crafts or hobbies like stamp and coin collecting, painting, drawing, or other artwor, woodworking, writing letters, playing cards, playing board games like Checkers, Chess, Monopoly and Scrabble, doing home repairs and knitting or needlework are activities that may be protective if done regularly.
Drug Development Costs
The brain of a person with Alzheimer's disease is covered with deposits called plaques. There are scientists that believe these plaques form because of an enzyme, known as "molecular scissors". This enzyme cuts up a larger protein, making tiny fragments that stick together in tangled clumps. While not all scientists accept plaques as the cause of Alzheimer's disease, some consider them "smoking guns" because they are present early o and because they kill brain cells.
Scientists at Amgen Pharmaceuticals isolated beta secretase, the enzyme they think takes the first snip at the protein that eventually produces plaques. It is hoped that if the enzyme can be blocked, Alzheimer's disease may be halted and are testing compounds that block it. At best, though it could still be another 10 years before an effective therapy is found.
There is a great divide between researchers and people waiting for cures. A cure that is 10 years away is just around the corner to a scientist, but to patients and family members 10 years is an eternity.
An understanding of the time involved in developing a drug therapy such as the one Amgen is working is essential. Here is a quick look at the process. EIght to sixteen years is needed for a drug to go from basic discovery stage to our medicine cabinets. Approximately two years of planning and development is necessary before the search for the enzyme could even begin. Several more years will be needed for scientists to mae sure that they have the correct enzyme. Screening potential drug candidate will take another two years and then it has to be tested in animals to make certain that it's safe and effective.
If a drug survives the first 4-8 years of development, then it must go through three phases of clinical trials. All of these trials must be successful before application to the FDA can be made. Each of these steps cost $10-20 million, which brings the total for developing one drug to $200-400 million.
Nine out of ten drugs fail at some point and the company has to absorb that cost.
The above technical information was based upon Press Releases of the Alzheimer's Association.
