Alzheimer Related News Items

News as of 10/08/00
For more info on these abstracts write/call Ed Cabic (edcabic@home.net or 410-992-7197)
For more AD information, see Alzheimer Information athttp://www.connext.net/~seniors/infoad.htm
Copies of these reports are posted there
This web page was started at the Florence Bain Senior Center in Columbia MD

Top Items
AD Vaccine Proves Successful in Mice - Scientists at Brigham and Women's Hospital in Boston, Massachusetts report a vaccine of amyloid-[beta] peptide, administered nasally, may prove successful in reducing the accumulation of the debilitating amyloid plaques in AD. The treatment, which has previously been tested in an injection form, "creates a new avenue for treating the disease because it takes an immunological approach," lead author Dr. Howard L. Weiner told Reuters Health. In this study using mice, the vaccine was shown to stimulate the immune system to produce antibodies that bind to the amyloid fragments and "clear them out of the brain," according to Weiner. The investigators have so far tested the vaccine in a special strain of mice that have been bred to develop plaques similar to those seen in human AD. The vaccine was able to reduce the build-up of plaques by as much as 60%, according to the researchers. "We expect to have our nasal vaccine in clinical trials sometime next year," Weiner said. By Keith Mulvihill Reuters Health 9/28/00

Study Finds Key Link Between AD Genes and Cellular Defect - A research team based at Massachusetts General Hospital (MGH) has discovered a key link between two cellular abnormalities associated with early-onset AD. They are mutations in genes for proteins called presenilins and an altered handling of calcium inside cells. The researchers have tied a specific calcium pathway to the production of amyloid-beta42, the sticky protein fragments that make up the plaques found in the brains of people with the disease. The findings, which also suggest a normal function for the presenilin proteins, identify a new target for drugs that may prevent or treat the devastating disease. The researchers report that the presenilins appear to control a process that regulates the level of calcium in a cellular compartment called the endoplasmic reticulum and that presenilin mutations known to be associated with inherited AD slow down this regulatory process. They also show that inhibiting this particular calcium pathway increases production of amyloid-beta42 (A-beta42). "We have found the molecular basis of the altered calcium metabolism previously observed in neurons expressing AD-associated versions of presenilin," says Tae-Wan Kim, the paper's senior author. Rudolph Tanzi, adds, "Our work predicts that, if you could develop a drug that stimulates this specific calcium pathway, you could lower levels of A-beta42, which is the name of the game in AD drug therapy development." Many cellular activities are triggered when signalling molecules bind to receptors on the cell surface, setting off a process called signal transduction. A key step in signal transduction involves release of calcium stored in the endoplasmic reticulum (ER) into the body of the cell, which helps translate the signal into a cellular activity. Once the calcium has been released, the supply in the ER must be replenished - much as an electronic camera flash has to recharge after firing. Movement of calcium from outside the cell into the ER utilizes a recently recognized pathway called capacitated calcium entry (CCE). The processes that control CCE, which differs from other modes of moving calcium into or out of the cell, are still being investigated. To test whether inhibition of CCE had an impact on the deposition of A-beta, the researchers used cells that overproduce the amyloid precursor protein and as a result A-beta. They applied the three calcium pathways inhibitors and found that inhibition of the CCE pathway led to increased production of A-beta42, compared with the more common version of the fragment, called A-beta40. The other calcium pathway inhibitors had no effect on the cells' A-beta production. "If we can find compounds that increase CCE just enough to lower A-beta42, we may be able to offer a way to prevent or slow down the progression of AD to members of families effected by these mutations, some of whom begin to show symptoms at a very young age," Tanzi says. "While we currently don't know whether this information also might be applied to the late-onset, non-inherited type of AD, we would assume that the pathways that go wrong in early-onset illness also are involved in late-onset disease." PR 9/27/00

 

Drugs
Aricept Better Tolerated than Exelon in Patients with Mild to Moderate AD - Results from the first head-to-head study between Aricept® (donepezil hydrochloride) (Eisai and Pfizer Inc) and Exelon® (rivastigmine tartrate) (Novartis Pharma AG) showed that in this open-label study Aricept was better tolerated than Exelon in patients with mild to moderate AD. Data were presented at a scientific conference earlier in 9/00 in Munich, Germany. "Despite the often devastating nature of the disease, tolerability is still very important to patients with AD," said David Wilkinson, MD, director of the Memory Assessment and Research Centre, Moorgreen Hospital, Southampton, England, and an investigator in the study. "Patients tend to be elderly and often have other medical conditions that can make treating AD more complex. It is therefore important to treat patients with medications that are well tolerated and easy to use, such as Aricept." Key study findings included almost 4 times as many patients in the Exelon-treatment group reported nausea compared with the Aricept-treatment group (41.8% vs 10.7%). Three times as many patients in the Exelon-treatment group reported vomiting compared with the Aricept-treatment group (23.6% vs 7.1%). Twice as many patients in the Exelon-treatment group discontinued treatment due to side effects compared with the Aricept-treatment group (21.8% vs 10.7%). Almost twice as many patients were able to remain at the maximum daily dose of Aricept, 10 mg once a day, than the maximum daily dose of Exelon, 12 mg daily (6 mg twice a day) (87.5% vs 47.3%). Physicians were surveyed about their overall satisfaction with study medication for each patient. Physicians reported being "very satisfied" with study medication for twice as many Aricept-treated as Exelon-treated patients (46.4% of Aricept-treated patients; 18.9% of Exelon-treated patients). PR 9/227/00

Wyeth Licenses CAT AD Antibodies - Cambridge Antibody Technology Plc said 9/14/00 it had granted Wyeth-Ayerst Research an exclusive product licence to develop antibody drugs for AD, a hot area of research for drug firms. The antibody treatment, which is in pre-clinical development, is targeted at the amyloid peptide which forms plaques found in brains of people who died from AD. CAT believes its antibodies -- proteins which bind to specific substances in the body -- can play a key role in tackling the degenerative brain disease. Earlier this year Wyeth-Ayerst announced an alliance with Ireland's Elan Corp to develop anti-AD agents and the two companies will now apply CAT's technology to this work. By Ben Hirschler Reuters 9/14/00

Canadian Firm to Start AD Trials in S. Africa - Canadian biotech company Immune Network Research said 9/12/00 it expected to begin trial treatments of AD patients later this year in South Africa, using a drug dapsone mostly used against leprosy. Immune Network President Allen Bain said the trials of the drug dapsone, which are being carried out with CroMedica Global, Inc, would also be conducted in Poland, Brazil and Israel. Dapsone, a generic anti-inflammatory drug, is used to treat AIDS-related symptoms as well as leprosy. Bain said his company was now developing a new composition based on dapsone to stem the progression of AD. Bain said the dapsone project sought to stem the inflammation associated with the disease, which he said was the real cause of damage to the brain. Bain was optimistic about the success of the drug, saying the trials were strongly supported by evidence from a retrospective study of 3,700 Japanese leprosy patients which found that leprosy patients who were regularly treated with dapsone rarely suffered from AD. "With dapsone and our composition which is based on dapsone we have a 40-year history of understanding what can go wrong with the drug...The toxicity has been known for 40 years and the toxicity is mild enough that the physicians involved in this trial are able to go ahead with the trial" he said. By Emelia Sithole Reuters 9/12/00

Blood Pressure Drugs May Also Reduce Dementia Risk - Drugs that reduce the risk of arterial diseases, such as those that lower blood pressure, reduce blood cholesterol levels, prevent dangerous blood clots, and treat diabetes, may also help to reduce the risk of dementia in older adults, according to a study by researchers at the Indiana University School of Medicine. By reducing the risk of arterial disease, these medications help to maintain blood flow to the brain. This appears to cut the risk of intellectual impairment in the elderly, including the risk of AD. "There is growing evidence that cerebrovascular disease may contribute to the develop-ment, progression and presentation of AD," said Dr. Hugh C. Hendrie one of the study authors to Reuters Health. When they looked at each of these drugs separately, Hendrie explained, the study authors found that antihypertensives or blood pressure medications showed the greatest ability to protect mental capabilities such as memory, reasoning and judgment. The authors admitted that the study does not show whether the effects on mental functioning were the direct result of effects from the medications or the result of other factors that can contribute to how well a person functions. "For example, older people who visit doctors and take medications may also adhere to a healthier diet," they point out. "It is possible that cognitively impaired or demented individuals underutilize medical services." The research team plans to conduct more studies to examine the long-term effects of these drugs. By Chris Cunningham Reuters Health 9/11/00 Journal of the American Geriatrics Society 2000; 48:1035-1041

Phytopharm Tests Asian Plant Drug for AD - Phytopharm Plc, a UK biotechnology company specializing in making medicines from plant extracts, said 9/11/00 it had started clinical trials on a new drug for senile dementia derived from an Asian plant. The company is keeping details under wraps, pending patent approval, but Chief Executive Richard Dixey said a tonic extracted from the plant was used as a traditional herbal medicine in Asia. Phytopharm has isolated the active molecule in the plant and found a way to make it synthetically from a readily accessible chemical intermediate. The product, P58, increases the production of receptors in the brain which allow nerve cells to communicate with each other, making it potentially useful in treating AD and other senile dementias, including Parkinson's disease. "It's an extremely important drug for us...P58 has the potential to become the first in a new therapeutic class capable of reversing the underlying loss of nerve receptors," Dixey said. The adult brain contains approximately two trillion nerve cells, each of which has some 100,000 receptors on its surface. However, after the age of 40, scientists estimate people lose about 20 percent of these receptors, resulting in a gradual decline in cognitive performance. By Ben Hirschler Reuters 9/11/00

Axonyx Sets Phase II Trial for AD Drug - Axonyx Inc. said 9/12/00 it had completed safety trials for its lead AD treatment and plans to begin Phase II trials before the end of the year. The biotech company said it identified a therapeutic range for the oral administration of multiple doses of the AD treatment, called Phenserine, in a Phase I human safety trial. The study follows the company's successful single-dose Phase I trial. The second Phase I trial confirmed preclinical findings that Phenserine demonstrated patient safety and showed a significant inhibition of red blood cell acetylcholinesterase, Axonyx said. Inhibition of this enzyme in brain is associated with improvement of memory and cognition in patients with AD. Reuters 9/12/00

UK Scientists Turn to Chinese Medicine for New Cures - British scientists are turning to traditional Chinese medicine and using extracts from sage and other plants to develop new treatments for AD and pelvic pain, they reported 9/11/00. Professor John Wilkinson of Middlesex University is developing a potential treatment for AD from sage extract. Wilkinson and his colleagues are using traditional herbs, robotic systems and computer technology to test the effects of thousands of different plant extracts. They have tested purified compounds from sage extract to see if they inhibit an enzyme called acetyl cholinesterase. The amount of the enzyme in the brain is thought to be linked to memory loss in AD. "What we are doing is trying to develop a herbal extract which could be used as an acetyl cholinesterase inhibitor for AD and other areas of the brain," he said. By Patricia Reaney Reuters 9/11/00

Elan Pharmaceuticals Has Irish Luck - In 1999 Dublin-based Elan Pharmaceuticals bought San Francisco's Athena Neurosciences for $600 million. Athena was founded in 1987 by a Harvard Medical School professor, Dennis Selkoe, and a venture capitalist, Kevin Kinsella. It had a lofty goal: to cure AD. In 1996, it had sales of $54 million. Other acquisitions followed, each giving Elan access to a new market. "What they were looking for was a diamond in the rough," said Ivan Leiberburg. Elan's shiniest diamond may be the AD vaccine developed by Athena Neurosciences. The vaccine chased the plaques of dead cells that are the hallmark of the disease out of mouse brains, and it may do the same in humans. There are 4 million AD patients in the U.S. alone. If the drug works in humans, it would easily be worth billions when it goes on the market, probably in 2004 or 2005. By Matthew Herper Forbes.com 9/18/00

 

Genes & Genetic Issues
Researchers Find Evidence of a New AD Gene - An unexpected incidence of AD in one Arab community of Wadi Ara in Isreal has led researchers to the first evidence that a recessive gene is involved in the degenerative brain disorder. Among elderly residents of Wadi Ara 60% of the people older than 85 have AD as compared with a rate of about 40% elsewhere in the world. Because Wadi Ara residents frequently marry within their families, the researchers were able to uncover unusual genetic roots to the residents' AD cases. Scientists had previously known of a link between a variant of a gene called apoE to an increased AD risk where - - about 15% of people in the general population carry this variant. In this study, however, the researchers found that less than 4% of Wadi Ara residents carry the variant. The researchers conclude the apoE-4 variant cannot explain the community's high prevalence of AD. The researchers speculate that a recessive gene may be the culprit. Because traits carried on recessive genes are masked by those of dominant genes, a person must inherit the recessive gene from both parents for the trait to manifest itself. Since Wadi Ara residents often marry relatives, the chances of their inheriting a recessive trait are higher than average. Study co-author Dr. Robert P. Friedland told Reuters Health that it is possible a recessive gene plays a role in AD in other populations, but such genes are tough to find in heterogeneous groups. Nevertheless, the search is under way, said Friedland, an associate professor of neurology at Case Western Reserve University in Cleveland, Ohio. Reuters Health 9/11/00 Neurology 2000;55:731

'Chips' Dip Into Brain Behavior - One-inch-square glass wafers that can contain 10,000 genes called a gene chip could someday help scientists protect your brain cells from the trauma of a seizure, the shaking of Parkinson's or the mental decay of AD. Using this new gene chip technology, researchers at the Salk Institute for Biological Studies in La Jolla, Calif., compared the entire lineup of genes in two types of mice to find out how gene behavior differed between each strain during a seizure. For this study, they used chips containing the 13,000 known genes for mice. The two strains of mice differed in one important aspect. In one, many brain cells died when a seizure was triggered; in the other, relatively few brain cells died. The scientists found about 70 genes that showed different levels of activation between the two strains of mice. "Now what we have are some candidates. We can start understanding which of these candidates are responsible for specific ways that those two very different strains of mice are," says Dr. Carrolee Barlow one of the researchers. "We have a handful of genes that might make these mice so different from each other." Barlow says these findings could also be relevant to neurological disorders such as AD and Parkinson's. By Nicolle Charbonneau HealthSCOUT 9/25/00  Proc. Natl. Acad. Sci. vol. 97, 11038-11043 9/26/00 For more on gene chips see  http://www.Gene-Chips.com .

Scientists Turn Adult Brain Cells to Muscle - As the politics surrounding stem cell research grows more contentious, scientists have found yet more evidence that stem cells collected from adults can be used to manufacture a range of body tissue--a feat once thought to be unique to embryonic stem cells. However, researchers report, there is still no evidence that stem cells from adults are as promising in treating disease as those from embryos. In experiments with cells from mice and humans, Italian researchers have been able to coax brain stem cells to give rise to muscle. Stem cells are primitive cells that generate a wide range of body tissue, leading scientists to speculate that stem cells could be used to replace deteriorating tissue in people with AD, Parkinson's and other degenerative conditions. "There is still no indication that adult stem cells are as plastic, or pliable, as embryonic cells," lead study author Dr. Angelo L. Vescovi told Reuters Health. What does seem clear is that adult stem cells from one type of tissue can be pushed to generate other types of tissue, according to Vescovi, a researcher at the Stem Cell Research Institute in Milan, Italy. Dr. Charles Jennings, editor of Nature Neuroscience and author of an editorial accompanying the report, in an interview with Reuters Health emphasized that too little is known about the potential of adult stem cells to known if they are as promising as embryonic stem cells for treating disease. "It's an overstatement to say adult stem cells can do it all," Jennings said. "It is disturbing to see people citing scientific evidence out of context for political purposes." By Amy Norton Reuters Health 9/19/00 Nature Neuroscience 2000;3: 961-962, 986-991

Scientists Spar over Stem Cell Research - A top researcher studying the potential of adult stem cells told a US Senate subcommittee 9/14/00 that the federal government should also fund research using stem cells derived from human embryos. "If our therapies work, we will not need fetal tissues nor will we need to introduce foreign cells into a patient," Dr. Darwin Prockop, director of the Tulane University Center for Gene Therapy, told the Senate Appropriations Subcommittee on Labor, Health and Human Services, and Education. Prockop and others in his laboratory have been studying the use of adult stem cells in neurological ailments including Parkinson's disease, AD, stroke, and multiple sclerosis. But even with the promise, "we're not there yet, Prockop told the subcommittee. Because it will be at least two years before the first human trials using adult stem cells can be performed, he said, "in my opinion it would be a serious mistake to stop all research on human embryonic cells and tissues because of the exciting discoveries my laboratory and others have recently made about adult stem cells. We are simply not ready for a moon shot-like strategy in which we place all our bets on adult stem cells." That placed Prockop at odds with those who want Congress to explicitly forbid the use of federal funds for research using embryonic stem cells. They have argued that adult stem cell research is equally promising as that using cells from embryos, without the ethical problems. Currently, the National Institutes of Health has interpreted the Congressional ban on research using embryos not to cover stem cells derived from embryos, as long as those cells are not removed using federal funds. By Julie Rovner Reuters Health 9/15/00

 

Caregivers
Isolation and Strain: Families of AD Patients Can Be Victims, Too - As the number of U.S. AD patients climbs past 4 million, the ranks of beleaguered care-giving relatives also swell -- millions of elderly spouses or grown children whose burdens make them highly vulnerable to emotional, physical and financial strain. Beyond the expenses, caregivers face a higher-than- average risk of depression, stress and ill health. Elderly people strained by caring for an ailing spouse were 63 percent more likely to die within four years than other spouses, according to a University of Pittsburgh study. At the Alzheimer's Association's New York City chapter, education and training coordinator Paulette Michaud presided over a recent meeting for family caregivers, urging them to join one of the city's many support groups. "People in support groups do better than those who don't join," she said. Later in the evening, at a session with four caregiver families, she empathized when they complained about doctors who lacked expertise in coping with AD. "Doctors do feel impotent around this disease," Michaud said, urging the families to shop for a physician. "This illness is too long a process for you to suffer through medical advice that isn't useful to you." Nancy Reagan, in a newly published book, voices the sentiments of many AD caregivers as she describes the effect of the degenerative brain disease on her husband, Ronald Reagan. "You know that it's a progressive disease and that there's no place to go but down, no light at the end of the tunnel" she writes. "You get tired and frustrated, because you have no control and you feel helpless." As to the role played by family caregivers, Vice President Al Gore has proposed a $3,000 per year tax credit to help compensate them, saying their sacrifices "are almost impossible to imagine." His Republican rival, George W. Bush, has proposed a 100 percent tax deduction for long-term care insurance premiums. Judy Riggs of the Alzheimer's Association says none of the current proposals comes close to meeting the mounting costs. She suggests that long-term health care eventually will have to be covered by broad-based health insurance plans, the same way acute medical care is now. "It's important that people pushing these proposals understand -- the problem won't go away," Riggs said. AP 9/25/00

 

Prevention
Carrots Have More Antioxidants When Cooked - While carrots are always a healthy food choice, recent findings by researchers at the University of Arkansas suggest that cooking and mashing them up may increase their nutritional value. According to a study presented at a recent meeting of the American Chemical Society, the level of antioxidants in carrots that were cooked and pureed was more than three-times higher than levels of the compound measured in raw carrots. Antioxidants are compounds in food that prevent damage to cells caused by free radicals, natural byproducts of metabolism that can destroy the DNA of cells. Studies have shown that antioxidants may help prevent chronic diseases such as cancer and AD. "Many consumers think that fresh vegetables are always superior in nutritional quality than processed vegetables but this does not appear to be true for carrots," Luke Howard, the study's lead author, told Reuters Health. Researchers stressed that additional studies are needed to determine if antioxidants in processed carrots are well absorbed in the human body and can prevent free radical damage to human tissues. By Suzanne Rostler Reuters Health 8/30/00

 

Other Items
Bush Seeks More Funds for Disease - George W. Bush, courting seniors in a must-win state for Republicans, proposed spending an additional $67 billion over the decade to search for cures for age-old afflictions, including AD and many forms of cancer. "As president, I will fund and lead a medical moonshot to reach far beyond what seems possible today," Bush said in a speech 9/22/00 at a retirement community Sun City, Florida. At the Sun City Center Bush told a predominantly elderly audience that, if elected, he would "promote medical advances with new resources and new resolve." Specifically, Bush would complete a five-year plan already in progress in Congress to double NIH funding by 2003, to about $27 billion. Then, he proposes to keep that budget growing at the same pace for the rest of the decade - roughly 15 percent a year. Highlighting diseases of the elderly, Bush said, "Four million Americans, including a beloved former president, live in the fading light called AD." Former President Ronald Reagan is suffering from the disease. "Help is on the way," Bush said. Medical research has broad bipartisan support in Congress. In fact, Congress has approved higher spending on it than President Clinton has proposed each year since legislative action started in 1997 to double the NIH budget. By Tom Raum, AP 9/22/00