Alzheimer Related News Items

News as of 3/05/00
For more info on these abstracts write/call Ed Cabic (edcabic@home.net or 410-992-7197)
For more AD information, see Alzheimer Information at http://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
Brain Cell Research Offers Hope for AD - Taking cells from a region of the brain known as the hippocampus, an international team of researchers have grown functional brain cells in lab cultures. The findings may have profound implications for restoring damaged or degenerative brain cells, which occurs in diseases such as AD and Parkinson's. The brain has recently been shown to regenerate some of its cells, but scientists were unable to identify the cells, known as stem cells, that gave rise to the new brain neurons. The technique used in this study now gives scientists the ability to identify those stem cells in the brains of living patients, and shows that these cells can be stimulated to turn into new neurons, principal author Dr. Steven A. Goldman of Cornell University Medical College in New York told Reuters Health. In addition, it may lead to the development of drugs that would stimulate the formation of new brain cells in people with AD or other diseases where brain cells degenerate, he commented. Goldman noted that the use of drugs to stimulate proliferation of new brain cells will probably result in a more successful strategy than attempting to grow the cells outside the body and then placing them back into the brains of patients, as some scientists have suggested. By Steve Mitchell Reuters Health 2/28/00 Nature Medicine 2000;6: 271-277

Inflammation-related Gene Triples AD Risk - People with one of two natural variations in certain genes appear to be at much higher risk of developing AD, researchers report. The genes make interleukin-1 (IL-1), an inflammation-promoting protein produced by the immune system. There are two different versions of IL-1 -- interleukin-1 alpha (IL-A) and interleukin 1-beta (IL-1B). Dr. Sue T. Griffin and her team from the Central Arkansas Veterans Healthcare System in Little Rock looked at a specific variation in the gene for IL-1A (IL-1A2). Those people who have two copies of IL-1A2 -- one from each parent -- have three times the risk of the memory-robbing disorder than those with other versions of the gene. Those who have two copies of IL-1A2 in addition to a second variation in IL-1B (IL-1B2) are more than 10 times as likely to have AD, according to the report in the March issue of the Annals of Neurology. The researchers compared the genetic makeup of 232 people with AD to 167 people without the disease. Overall, 13% of those with AD had two copies of IL-1A2 compared with 7% of those without the disease. A variation in IL-1A also appears to be linked to the development of AD at an earlier age. In a second study in the same journal, Griffin, Dr. Luigi Grimaldi from the University of Milan, Italy, and colleagues found that people who had an IL-1A variation were almost five times as likely as others to develop AD before the age of 65 years. Those with an IL-1B variation had nearly double the risk of developing the disease early on. Overall, people with the IL-1A variation developed AD 9 years earlier than people with other forms of the gene. "These results clearly demonstrate an association of (certain IL-1 genes) with AD,'' Griffin said. "Armed with this information, we can work toward treatments that prevent AD or treat it once it occurs." Griffin added "This also helps to explain why earlier studies showed that anti-inflam-matory drugs delay the onset of AD in some patients. We need to do more studies to determine how anti-inflammatory drugs might best be used to prevent AD." Reuters Health 3/02/00 Annals of Neurology 2000;47:361-365, 365-368

Guilford Licenses Novel Discovery From Johns Hopkins University - Guilford Pharmaceuticals Inc. announced 2/16/00 that it has licensed a discovery from the Johns Hopkins University relating to a unique biological target, serine racemase, that could be used to develop treatments for neurodegenerative diseases. "This is an exciting discovery because serine racemase represents a novel way to potentially block the harmful effects of glutamate over-stimulation," remarked Dr. Solomon H. Snyder, Director of Neuroscience at the Johns Hopkins University School of Medicine. The overproduction of glutamate has been implicated in a large number of acute and chronic degenerative conditions including stroke, epilepsy, peripheral neuropathies, chronic pain and Parkinson's, AD and Huntington's disease. Glutamate is one of the most abundant amino acids in the body. Scientists believe that the harmful effects of excessive glutamate occur principally through activation of a subtype of the glutamate receptor called the NMDA receptor. NMDA receptors have not one, but two sites that must be activated in order for neurotransmission to take place. Recently scientists at Johns Hopkins, led by Dr. Snyder, discovered that the D-isomer of the amino acid, serine (D-serine), was the principal activator of this site. Dr. Snyder's lab was responsible for isolating and cloning the enzyme, serine racemase, which converts the L-isomer to the D-isomer. The Hopkins group discovered that D-serine, acting in tandem with glutamate, is required for NMDA activation. This discovery provides them with a new biological target for drug development, since small molecule inhibitors of serine racemase could be anticipated to prevent glutamate neurotoxicity in conditions like stroke and other neurodegenerative conditions. Dr. Peter Suzdak at Guilford said "The over-stimulation of NMDA receptors by glutamate is believed to be an important initial pathologic event in stroke and several neurodegenerative diseases. Finding an alternative method of blocking glutamate activation of the NMDA receptor -- by selectively blocking the synthesis of D-serine -- could potentially offer new treatment alternatives for conditions like stroke and chronic degenerative disorders like Parkinson's and AD. We are excited about pursuing this novel approach as part of our neuroprotectant research and development program." PR 2/16/00

Drugs
Reminyl, a Novel AD Treatment, Receives First EU Approval - Reminyl® (galantamine), a new symptomatic treatment for dementia of the AD type, received its first regulatory approval within the European Union from Sweden, announced Janssen-Cilag and Shire Pharmaceuticals Group plc 3/3/00. Reminyl will subsequently be submitted through the EU Mutual Recognition Procedure to gain marketing approval in Europe. Like other therapies currently on the market, Reminyl boosts the levels of acetylcholine in the brain by blocking the action of the enzyme acetylcholinesterase. However, unlike other therapies, research indicates that Reminyl has a second mechanism of action: it acts on nicotinic receptors in the brain. The "modulation" of these receptors is thought to increase the release of acetylcholine. An important feature of AD is the progressive loss of cholinergic nerve cells, leading to a decline of critical chemical signals in the brain. PR 3/3/00

Compounds Slow 'Mad Cow-' Related Disease in Mice - A drug that slows the development of fatal prion diseases such as 'mad-cow' disease may be near, according to researchers from the National Institutes of Health. Mad cow disease is one of a group of disorders known as spongiform encephalopathies, which affect humans and animals. They are characterized by the progressive destruction of brain tissue and include such conditions as Creutzfeldt-Jakob disease, kuru, and scrapie. "In the... prion diseases, accumulation of an abnormal protein in the brains of infected individuals is a critical event in the disease," lead researcher Dr. Suzette Priola told Reuters Health. "If formation of this protein could be (prevented), it might be possible to prevent or even cure the disease." Priola's group had earlier identified a large class of chemical compounds called cyclic tetrapyrroles, which interfere with the formation of this protein. The team's findings may have implications beyond the treatment of the spongiform encephalopathies. ``It is also possible,'' Priola pointed out, "that other diseases which involve abnormal protein accumulation, such as AD, might be inhibited by certain cyclic tetrapyrroles." "Hopefully,'' Priola said, "our results will encourage other laboratories or even drug companies to start looking at the cyclic tetrapyrroles." By Penny Stern, MD Reuters Health 2/28/00 Science 2000;287:1503-1506

Steroids Do Not Slow Down AD - Even though inflammation in the brain has been linked to the progression of AD, low-dose treatment with the steroid prednisone, which has anti-inflam-matory effects, does not slow down the disease, new study findings from Georgetown University Medical Center in Washington, DC. show. But the results of the study do not necessarily mean that other medications that fight inflammation will not help people with AD, the study's lead author Dr. Paul S. Aisen told Reuters Health in an interview. Now that it is clear that low-dose prednisone is not helpful for people with AD, the next step is to test the effects of a class of medications called nonsteroidal anti-inflammatory drugs (NSAIDs), Aisen said. These drugs may help slow down AD, since they target an enzyme called cyclooxygenase that is thought to play a role in the disease, according to Aisen. By Merritt McKinney Reuters Health Neurology 2000;54:588-593, 732-734.

Neurogen Announces Progress in Its Drug Development Programs to Treat Anxiety and AD - Neurogen Corp. announced 2/17/00 progress in its clinical development drug programs to treat anxiety and AD. Neurogen and Pfizer are collaborating to develop drugs to treat AD. The collaboration has yielded drug candidates designed to enhance cognition by acting in the brain's memory centers as highly selective inverse agonists of specific GABA receptor subtypes. Drug candidates from the collaboration improve memory in a variety of laboratory animal models. In preparation for Phase II studies in the US, an Investigational New Drug Application (IND) was filed by Pfizer with the FDA and has recently become effective. Multiple dosing Phase I studies examining the safety and pharmacokinetics of the collaboration's most advanced drug candidate in healthy young and elderly human volunteers are nearing completion in Europe. Results of Phase I clinical trials conducted to date indicate that this compound is well-tolerated. PR 2/17/00

Aventis Pharma Discontinues Development of Propentofylline - Aventis Pharma, the pharmaceutical company of Aventis S.A., announced 3/3/00 that it is discontinuing development of propentofylline as a possible treatment for AD. A major contributing factor in the termination of propentofylline was the disappointing outcome of the recently completed Propentofylline Long-term Use Study (PLUS). In the 72-week, Phase IIIb study, there were no treatment differences detected between the study population treated with propentofylline and the population treated with placebo. PR 3/3/00

American Biogenetic Sciences' Neuroscience Compound Will Be Studied in AD Model - American Biogenetic Sciences, Inc. announced 3/2/00 that The Institute for the Study of Aging Inc. will fund a study on the ABS-205 neuroscience compound, an agent for treatment of AD. This drug candidate is in pre-clinical trials and the company believes it has enormous potential for the treatment of neurodegenerative disorders such as AD, as well as Parkinson's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), neuropathic pain, stroke and head trauma. The study will be done at, University College Dublin to determine the effects of ABS-205 in aged animal models using a spatial learning task, a model commonly employed to evaluate novel cognition-enhancing drugs. This is with a view evaluating the potential of ABS-205 for learning dysfunction associated with aging and AD. These experiments will build on previous work carried out at University College Dublin, Ireland, in which acute and chronic administration of ABS-205 has been shown to enhance spatial learning. PR 3/2/00

Neurogen Reports Progress in Installing AIDD Technology at Pfizer Inc - Neurogen, adrug discovery and development company, announced 2/22/00 that it has completed the first phase of the installation of its AIDD (Accelerated Intelligent Drug Discovery) system at Pfizer Inc. Neurogen's AIDD program integrates combinatorial compound synthesis, high throughput screening and advanced informatics to generate drug discovery data in a two-week period, a process that can otherwise take several months. Scientists can use the AIDD system, via a stand-alone system or incorporated into an existing drug discovery platform, to quickly and efficiently direct the discovery of new drug leads. Using the AIDD program, Neurogen has generated hits over the last five years in each of its drug discovery programs, including some programs where no drug leads were known to exist in the industry. Neurogen and Pfizer are also collaborating in human drug development programs to treat AD, anxiety, depression, insomnia, and obesity. In addition, the two companies are collaborating on drugs to treat dementia and anxiety in companion animals. PR 2/22/00

Scientists Gather for NeoTherapeutics' Research Conference On Neotrofin™ (AIT-082) - NeoTherapeutics, Inc. announced 2/22/00 that it held the First Annual AIT-082 Conference on February 4^th and 5^th, 2000. During the two-day conference, academic scientists and NeoTherapeutics' internal scientists presented data collected on the actions of AIT-082 (NEOTROFIN™, leteprinim potassium) in various models of nervous system deficits and diseases. The results of these studies may provide NeoTherapeutics with the necessary information for additional clinical applications for AIT-082. The data from this conference will be presented to the public in the form of research publications and presentations at research conferences over the next year. "The underlying conclusion from this conference was that the data on AIT-082 continues to support the theme of nerve regeneration," stated Alvin J. Glasky, Ph.D., President, CEO and Chief Scientific Officer of NeoTherapeutics. Human clinical studies have demonstrated positive effects of NEOTROFIN™ on memory and behavioral function in patients with AD. PR 2/22/00

Genes & Genetic Issues
AD Risk Factor Explained - Researchers at the Washington University School of Medicine in St. Louis, Missouri, and at the Lilly Research Laboratories in Indianapolis, Indiana, studied mice to explore how apolipoprotein E (apoE) influences amyloid-beta plaque-forming deposits in the brain. Their article shows that an interaction between apoE and amyloid-beta is critical not only for the buildup of amyloid-beta, but also for an important part of its toxicity in the brains of living animals. Dr. Steven M. Paul at Lilly explained to Reuters Health that the apoE gene is actually "a risk factor gene. If you have two copies of the E4-variant, you have about a 10-fold greater risk of getting AD.'" He added that "about half the people with two copies will get the disease by age 65 and about 80% will get it by age 85.'' In contrast, the presence of the apoE2 variant is protective and reduces the risk of AD. Studies such as these "indicate that modification of human apoE levels or interactions with amyloid-beta, will modify AD,'' said Dr. David M. Holtzman at Washington University which may open the way for innovative strategies to treat or perhaps prevent the disease. Dr. Paul concurs. "If we could find a way to reduce apoE expression, since we know what cells make it in the brain, we think we could come up with a drug that might prevent plaque deposition," he said. By Penny Stern, MD Reuters Health 3/2/00 Proceedings of the National Academy of Sciences Early Edition March 14, 2000

Liver Disease Strategy Unveiled - A novel approach to treating children with alpha1-antitrypsin deficiency, the most common genetic liver disease, is being studied by researchers at the Washington University School of Medicine in St. Louis. The proposed treatment involves using a drug, a "chemical chaperone," to force mutant forms of a protein out of cells. Once in the blood, this protein can help correct problems caused by the gene defect. It is known that chemical chaperones can effectively modify a defective protein by making structural changes to it. A number of potential chemical chaperones have been suggested and investigated in relation to other disorders. "This approach [of treatment with "chemical chaperones"] eventually could prevent these patients from needing liver or lung transplants,'' said senior study author Dr. David H. Perlmutter in a statement. He added that similar treatment might also help patients with other diseases, including AD, Parkinson's and Huntington's disease. "I think this approach could ultimately have a major impact on a number of disorders," noted Perlmutter. Reuters Health 2/17/00 Proceedings of the National Academy of Sciences 2000;97:1796-1801

Genes of Fruit Fly Unraveled - Scientists who hope to unravel the genetic blueprint of human beings say they have successfully tested out their methods on a much smaller subject - the fruit fly. The achievement, revealed 2/18/00, represents an important dry run of gene-sequencing methods that are aimed at tracking down all 70,000 or so genes inside every human cell. The researchers unraveled more than 97 percent of the fly's genetic code and more than 99 percent of the actual genes. In all, it turns out that every fruit fly cell contains 13,601 genes. The scientists have lumped the fruit fly genes into broad categories, such as those that contain the code for enzymes or for structural proteins. The duties of half of the genes are unknown, but the rest make proteins already familiar to scientists. The research team looked at 289 genetic flaws known to cause diseases in humans. Using the new data, they looked for similar genes in the fruit fly and found that 60 percent of the human genes match up. These include genes for such common human problems as kidney disease, AD and cancer. In fact, 70 percent of the genes known to cause human malignancy were found to exist in similar form in the fruit fly. Three scientific papers on the work have been submitted for publication in the journal Science. Much of the raw data are already available on the Internet at the National Library of Medicine's GenBank site. By Daniel Q. Haney AP Medical Editor 2/19/00

Need for Anti-Inflammatory Therapy in AD Identified by Gliatech Scientists - Gliatech Inc. announced 2/14/00 that an established mouse model of AD shows brain inflammation that is similar to that observed in AD patients. The AD brain is characterized by the presence of amyloid plaques, and these plaques can trigger glial cell activation which leads to an inflammatory response in the brain. Presently, AD research has been greatly aided by the development of transgenic mice strains that form amyloid plaques. However, it has been unclear whether these mice have the plaque-associated inflammation seen in AD. Gliatech scientists examined the brains of one of the AD transgenic mice strains for evidence of glial-mediated inflammation. This strain of mice is recognized for their age-dependent development of AD-like plaques. The researchers found within these mice a close association between amyloid  fibril-containing plaques and activated glial cells that expressed cytokines such as tumor necrosis factor alpha, interleukin-1 and interleukin-6. These cytokines can result in an inflammatory response in the brain. This is the first reported demonstration of a plaque-associated inflammatory response in an AD transgenic mouse model, and further validates the company's position that amyloid fibrils trigger glial cell activation that contributes to disease progression. PR 2/14/00

Exelixis Delivers Target for Screening to Pharmacia & Upjohn - Exelixis, Inc. announced 2/10/00 that it has achieved the first milestone in its alliance with Pharmacia & Upjohn AB, which is intended to identify novel targets in the area of AD and Metabolic Syndrome. The collaboration includes the utilization of technology developed from Exelixis' Mechanism of Action (MOA) Program in addition to its comparative genomics and model systems technologies. This research collaboration brings together Exelixis' proprietary approach with Pharmacia & Upjohn's experience in the development and commercialization of products in the therapeutic areas of CNS and Metabolic Disease. Exelixis, Inc.'s comparative genomics and model system genetics provides a rapid, efficient, and cost-effective way to move from DNA sequence data to knowledge about the function of genes and the proteins that they encode. The company's technologies focus on the identification and validation of novel screening targets and proteins and their function for the pharmaceutical, diagnostic, agricultural, and animal health industries. PR 2/10/00

NeoTherapeutics Announces Issuance of New Patent For Its Nerve Regeneration Platform Technology - NeoTherapeutics, Inc. announced 2/23/00 that the company has been issued a new U.S. Patent No. 6,027,936 (http://164.195.100.11/netahtml/srchnum.htm) covering a method for controlling the expression of genes to produce neurotrophic growth factors to stimulate nerve cell growth within the human body. "This patent covers one of the actions of NEOTROFIN™, that of causing nerve sprouting, which research studies suggest may lead to the formation of new nerve connections. The company believes this effect is of vital importance to the functional regenera- tion of the nervous system. NEOTROFIN™ is being developed for nerve repair and regenera- tion, with AD as its first clinical indication. Pre-clinical studies have demonstrated that NEOTROFIN™ causes the production of multiple natural nerve growth (neurotrophic) factors and restores function in animal models of cognitive decline, aging, neurodegeneration, and spinal cord injury. Human clinical studies have shown NEOTROFIN™ to be safe and tolerable and demonstrated its positive effects on memory and behavioral function in patients with AD. PR2/23/00

BIOQUAL Announces Award for AD Research Small Business Innovation Research --SBIR- Grant From the National Institutes of Health - The grant is to identify and characterize DNA sequence variation in chimpanzees at four genes that contain mutations implicated in the pathogenesis of AD. Some comparative research on AD-related genetic loci and their involvement in age-related cognitive dysfunction or neuroanatomical degeneration has been done in great apes. However, both the extent of DNA sequence variation and its role in aging-related neuropathology is poorly understood. Consequently, there is a need for more extensive comparative work involving population screening and DNA sequencing of the various AD related loci homologous genes in hominoid apes. This could help identify and characterize species specific mutations or conserved polymorphisms that influence cognitive or neurological degeneration. PR 3/2/00

Wyeth-Ayerst Signs Agreement with MIICRO, Inc. to Evaluate Effects of Estrogen on the Brain - MIICRO, Inc. announced 2/11/00 that it has entered into a contract with Wyeth-Ayerst Laboratories to conduct a neuroimaging study on Premarin®, the estrogen drug Wyeth is evaluating for the treatment of AD. This new study will compare the effects of Premarin to those of Pfizer's drug Aricept®, currently marketed for the treatment of AD. Additionally, the study will look at the combined effects of the two drugs. In a 1998 study the data showed Premarin affects the area in the brain associated with cognition and memory, which is a critical step in demonstrating estrogen may be beneficial in the prevention of AD. Recent scientific studies have demonstrated that estrogen influences cognitive function in women and may have a protective effect against dementias and other cognitive dysfunctions, such as AD. In addition, other studies have demonstrated increased benefits when estrogen is used in combination with an acetylcholinesterase inhibitor, such as Aricept. The new study MIICRO has designed will provide an important set of data in evaluating the effects of estrogen compounds as they relate to the treatment of AD. PR 2/11/00

Master the 'Body Basics' to Become a Team Antioxidant(SM) Superhero - Which antioxidants are associated with a healthy heart? Which may help boost the body's natural defenses against the sun? To obtain the answers to these questions about the benefits of antioxidants, Internet users can now visit http://www.freshstarts.com to take the just-launched Body Basics quiz. Guided by the cartooned members of Team Antioxidant the Body Basics quiz enables parents, teachers and children to test their nutrition IQ and learn how vitamin C, vitamin E and the carotenoids (beta-carotene, lutein and lycopene) impact different parts of the body. Both the Body Basics quiz and freshstarts.com were created by BASF Corp. The members of Team Antioxidant represent vitamins C, E and the carotenoids (beta-carotene, lutein and lycopene). These antioxidants can be found in fruits and vegetables and have been shown to protect cells from damaging free radicals that can lead to serious illnesses, such as lung, prostate and oral cancers, as well as AD and Parkinson's disease. PR 3/3/00 

Other Items
Possible Cause of Parkinson's Disease Uncovered - Abnormal accumulation of a protein normally found in the human brain may be responsible for neurodegenerative disorders like Parkinson's disease, according to a new study done at the University of California San Diego. The protein, alpha-synuclein, "is normally produced in the brain but when overexpressed, it may accumulate in the brain and lead to AD and Parkinson's," lead study author Dr. Eliezer Masliah told Reuters Health. In normal amounts, the protein appears to play a role in communication between nerve cells, but in high amounts, it "disrupts the function of (brain cells) and eventually kills them," he explained. This research may lead to treatments for Parkinson's and AD, Masliah commented. But he noted that because the protein is normally found in human brains and presumably plays a role in important functions, a drug that blocks the protein entirely would not be useful. "We need something that blocks the (accumulation) of the protein, but not something that blocks the function of the protein," he said. By Merritt McKinney Reuters Health Science 2000;287:1265-1269

Mrs. Reagan: Former President OK - Former first lady Nancy Reagan says her husband is "doing as well as can be expected" five years after being diagnosed with AD. "It's a progressive disease, so you don't get better,'' she said appearing by phone on CNN's "Larry King Live" on 2/4/00. The former president turns 89 on 2/06/00. AP 2/5/00

Researchers Test Mobile Phone Link to AD - A possible link between mobile phone radiation and AD is being tested on laboratory rats, the leader of a Swedish university research team said 2/11/00. Their tests show that albumin proteins leak through the brain blood barrier in animals exposed to the microwaves. Professor Leif Salford at Lund University said "I cannot say that mobile phones give AD. But we cannot rule it out." He added that any link with such a disease would take a long time to develop. The Lund team is investigating whether proteins the same size as albumin or smaller also could penetrate the blood brain barrier and cause diseases like AD. Reuters 2/11/00