September 2, 2005 Progress In The Search For Alzheimer's Medications There are one hundred pharmaceutical and biotechnology companies that have 176 new medications in development to combat the feared memory destroying condition, Alzheimer's. At least eight of them are in the final stages of testing. The first approach of drugs such as Aricept is to counteract the effects of cholinesterase, an enzyme that fouls up the communication between brain cells. The second approach is to prevent or remove the protein deposits called "amyloid plaques" which also disrupt the working of brain cells. One of the newer investigations involves a protein called KDI tri-peptide (KDI) that can block the harmful effects of a substance called glutamate that is present in all degenerative brain diseases and spinal cord injuries. It causes permanent cell death and prevents the repair of damaged nerve connections. Glutamate is produced as part of the body's natural reaction to central nervous system damage. Human clinical trials are expected to begin soon. No toxic side effects have been seen in studies so far, and the Finnish researchers do not expect any since KDI occurs naturally in the human body. Serotonin (5-HT) widely distributed in animals and plants, is another target of research. A chemical messenger between nerve cells, it is perhaps the most implicated in cause and treatment of various central nervous system disorders including pain, migraine anxiety and depression. Researchers at Northwestern University have developed a new class of serotonin compounds called aminopyridazines. They are believed to treat and perhaps prevent inflammation of nerve cells in Alzheimer's. These compounds inhibit over-activation of glia, important cells of the central nervous system that normally help the body mount a response to injury or developmental changes but are overactivated in certain brain cells involved in degenerative diseases such as Alzheimer's. IT MAY NOT BE ALZHEIMER'S An estimated 15 to 25 percent of patients diagnosed as having Alzheimer's don't have it. The problem is that current diagnostic tests to detect Alzheimer's and other dementias are limited and the only way to confirm a diagnosis of Alzheimer's disease is examination of brain tissue after death. Living patients are assumed to have Alzheimer's by eliminating other possible causes of their symptoms -- an inaccurate method that often results in errors .The University of Oxford and Amersham International plc announced today a licensing agreement for an agent to be used in the living patients to diagnose Alzheimer's disease. Ceretec(R) (technetium Tc-99m) is a brain imaging agent developed by Amersham. It is now marketed for stroke worldwide and for dementia in Europe. The agreement allows Amersham to file a Supplemental New Drug Application (SNDA) with the U.S. Food And Drug Administration for the use of Ceretec(R) in diagnosing neurodegenerative disorders of the Alzheimer's type. So the race is on to find pharmaceuticals that will prevent or treat Alzheimer's as "Baby Boomers" become senior citizens. The term "baby boomer" was coined to describe the population explosion that occurred from 1946 to 1964, after U.S. soldiers returned from World War II and before birth control became widespread. Now, as the oldest boomers approach their 60s, they are harbingers of a health care trend that is expected to see the number of Alzheimer's sufferers soar from today's 4.5 million to between 11 million and 16 million by 2050. The costs of caring for that many Alzheimer's patients will be devastating. Just dealing with today's victims costs at least $100 billion a year in direct and indirect expenses, according to federal estimates. And those are merely dollars. They don't begin to estimate the emotional toll. WHILE WAITING FOR A BREAKTHROUGH In the meantime, consuming enough of the B vitamin folic acid significantly reduces the risk of Alzheimer's disease, according to a study appearing in the July issue of Alzheimer's & Dementia: The Journal of the Alzheimer's Association. "This report bolsters evidence that adequate folic acid may help the brain, nervous system and heart and blood vessels in a variety of ways," says William H. Thies, Ph.D., Alzheimer's Association vice president, medical and scientific affairs. "Since 1998, breads, cereals and other grain products have been fortified with folic acid in the United States to reduce the likelihood of serious nervous system birth defects. It's looking increasingly as if folic acid remains important for brain health throughout life." This study, published in the inaugural issue of the Alzheimer's Association official journal, found that older adults who consume at least the recommended dietary allowance (RDA) of 400 micrograms of folic acid per day reduced their risk of Alzheimer's by more than 50 percent. There was little added benefit from folic acid intake much above the RDA. Most study participants who met or exceeded the RDA did so through a combination of foods and supplements. Foods rich in folic acid include fortified bread products, green leafy vegetables, fruits, whole grains, and peas and beans. Researchers analyzed diet and supplement use for 579 participants in the Baltimore Longitudinal Study of Aging, a long-running federally funded investigation of the effects of growing older, and then followed them for an average of nine years to track incidence of Alzheimer's disease. Adequate folic acid has also been shown to lower levels of the protein building block homocysteine. Elevated homocysteine is a risk factor for heart attacks and diseases of the blood vessels and possibly Alzheimer's disease. Another B vitamin has also been found to be important to brain function. A deficiency of B12 often manifests itself first in the development of neurological dysfunction that is almost indistinguishable from senile dementia and Alzheimer's disease. Therefore, a number of patients exhibiting symptoms of Alzheimer's actually suffer from a vitamin B12 deficiency. Their symptoms may be reversible through effective supplementation. Among healthy people over the age of 75, furthermore, with a gene that makes them at higher risk for Alzheimer's, if they have low levels of vitamin B12, they do significantly worse on memory tests. This finding was reported in Neuropsychology, which is published by the American Psychological Association (APA). ***
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