Alzheimer Related News Items

News as of 6/05/99
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Top Item
Novartis Receives FDA Approvable Letter For New Therapy to Treat AD - Novartis Pharmaceuticals Corp. announced 5/13 that it received an approvable letter from the U.S. Food and Drug Administration (FDA) for Exelon® (rivastigmine tartrate capsules), a new drug to treat mild to moderate AD. An approvable letter usually represents the final step before a product receives FDA clearance for marketing in the United States. They expect approval by the end of this year. The 6-month clinical trials with Exelon demonstrate that patients taking Exelon showed improvement in cognition and global evaluation (based on assessments of cognition, behavior and functioning) compared to those on placebo. Exelon is expected to reach peak sales of $550 million worldwide in 2003, with about 60 percent of those sales in the United States, according to drug analyst Terrence Norchi, M.D., of Sanford C. Bernstein. Aricept and Exelon are considered the second generation of drugs to treat the incurable brain disease that affects up to about four million people in the U.S. alone. The two drugs are reversible inhibitors of acetylcholinesterase, an enzyme that breaks down the neurotransmitter acetylcholine. Acetylcholine is associated with cognitive functions such as memory, learning and judgment. Aricept, launched worldwide in 1997, and Exelon, which has been cleared for marketing inalmost 50 countries, do not have the serious side effects, such as liver toxicity, associated with Cognex. Cognex was launched in late 1993 and had worldwide sales last year of $12 million. Aricept had sales of more than $380 million. There have been no head to head trials of Aricept and Exelon, Novartis said. PR and Reuters 5/13/99

Drugs
Drug Trials Hide Conflicts for Doctors - In this new industry of clinical research, patients have become commodities, bought and traded by testing companies and doctors. The number of private doctors in research since 1990 has almost tripled, and top recruiters can earn as much as $500,000 to $1 million a year. The industry treats research agreements as corporate secrets and contractually forbids doctors to disclose them. As a result, few people outside the industry, including government officials, have seen the contracts or know the magnitude of the money involved. In a 10-month investigation, The New York Times obtained such contracts and thousands of other confidential documents that present a view of the research industry that has never before been available. These records, and interviews with participants, reveal a system fueling a pharmaceutical renaissance, but fraught with conflicts of interest; that places a premium on speed and meeting quotas; that relies on government and private monitoring that can be easily fooled and that some researchers said is inadequate; and that secretly offers a share of the cash to other health professionals who might influence patients to join a study. At bottom, the only thing separating a trusting patient from a study that could be inappropriate or potentially harmful is the judgment of a doctor torn by these unseen conflicts and pressures. By Kurt Eichenwald and Gina Kolata New York Times 5/16/99

NeoTherapeutics and CSL Announce Significant Clinical Improvements Seen With New Drug for AD - Data from a recently completed Phase 2a clinical trial of NEOTROFIN™ in patients with AD was presented. In patients with AD, the NEOTROFIN™ treated group showed an improvement from baseline testing in the ADAS-cog, a measure of cognitive functioning, after 28 days of administration. Total ADAS-cog scores improved in 72% of patients receiving the 150 mg dose. "Improvements in memory function and behavior suggest that NEOTROFIN™ may have therapeutic benefit in patients with AD," said Dr. Targum the principle investigator in this clinical trial. He added, "Larger studies of longer duration with NEOTROFIN™ are needed to ascertain the sustained cognitive benefit of this drug and evaluate the potential to modify the progression of AD." PR 6/2/99

Cephalon Announces R&D Collaboration with Lundbeck To Develop Products for Neurodegenerative Diseases - Cephalon, Inc. announced 6/1 that it has entered into a collaborative agreement with H. Lundbeck A/S to discover, develop and market products to treat neurodegenerative diseases, such as Parkinson's disease and AD. The collaboration will focus on the development of receptor tyrosine kinase (RTK) inhibitors, a novel class of orally active, small molecules which inhibit specific kinases associated with the death of neurons. In preclinical studies, these molecules have been shown to promote neuronal survival in animal models of Parkinson's disease and AD. In AD and Parkinson's disease, as in other neurodegenerative disorders, the underlying pathology is a profound and irreplaceable neuronal death. Such neuronal loss is critically influenced by activation of the stress-activated protein (SAP) kinase pathway. CEP-1347 and Cephalon's RTK inhibitors selectively and potently inhibit key kinases within the SAP kinase pathway, thereby blocking cell death in neurons. In preclinical models of neurodegenerative diseases, these molecules enhance neuronal survival, support normal neurological function, and represent the first orally active molecules that have the potential to halt the progression of these devastating disorders. PR 6/1/99

Interview - Shire Scouting for Biotech Firms - Britain's Shire Pharmaceuticals Group Plc said 5/11 it was actively looking for medium-sized acquisitions in the European biotechnology market, especially firms with early-stage products in bone diseases and Central Nervous System disorders. Galantamine, found in daffodil bulbs and a potential treatment for AD, and one of Shire's potential blockbuster products was submitted for European marketing approval on March 1999. Shire and its partner, Janssen, a unit of Johnson & Johnson had recently held talks with the Food and Drug Administration of the U.S. and was targeting U.S. submission by the end of 1999. Submissions on galantamine will also be made in Canada, Australia, Norway, Switzerland and South Africa by the first half of this year. By Arindam Nag Reuters 5/11/99

Ontogeny and Oxford Asymmetry International (OAI) Announce Collaboration to Optimize Small Molecule Leads - Ontogeny to Gain Access to OAI's Combinatorial Chemistry Expertise - Ontogeny, Inc., a privately-held biotechnology company and leader in the field of developmental biology, announced 5/13 that it has entered into an agreement with Oxford Asymmetry International to optimize small molecule leads derived from Ontogeny's develop-mental pathway-based assays. In addition to providing Ontogeny with medicinal chemistry services, OAI will also give Ontogeny access to its combinatorial chemistry expertise. Ontogeny, Inc. is a privately-held company whose mission is to create therapeutics that will significantly improve the quality of life by activating the body's ability to repair and regenerate. The Company is developing therapeutics for neurological diseases including Parkinson's and AD, diabetes, bone and cartilage disorders including osteoarthritis and fractures, blood disorders and cancer. PR 5/13/99

Studies Find that Ampakines Are First Drugs to Specifically Target Affected Portions of the Brain - New studies of Ampakines®, a class of oral compounds in clinical trials for the treatment of schizophrenia and AD, indicate that the drugs act with unprecedented specificity for areas of the central nervous system directly related to behavioral abnormalities arising from neurological disturbances as disclosed to the 54th Annual Scientific Convention of the Society of Biological Psychiatry. Ampakines, including the lead drug, Ampalex®, are being developed by Cortex Pharmaceuticals, Inc. Pre-clinical results with Ampalex (CX516) suggest an unprecedented degree of specificity for a drug targeting central nervous system diseases. This new family of drugs called Ampakines® enhance or amplify glutamate communications in the brain. Ampakines amplify the effect of glutamate on a particular subset of receptors called AMPA receptors. Published studies demonstrate that Ampakines can dramatically enhance memory in elderly animals and humans. PR 5/14/99

Synaptic Pharmaceutical's Collaboration with Warner-Lambert in Galanin Research Ends - Synaptic Pharmaceutical Corp. announced 5/14 that its partner in the field of galanin drug discovery, Warner-Lambert Co., has decided not to enter into the second stage of the collaboration. Galanin receptors, which are widely distributed in the central nervous system and present in other organs, are believed to be useful drug targets for a variety of therapeutic indications. These include AD, depression, pain and endocrine disorders, such as diabetes, and obesity. Synaptic has discovered and cloned genes that code for galanin receptor subtypes and has filed patent applications relating to these discoveries. PR 5/14/99

Genes & Genetic Issues
Worm Enzyme May Help Extend Life - Biologists at Columbia University studied a nearly microscopic roundworm known as Caenorhabditis elegans. They identified an enzyme known as a cytosolic catalase that seems to act as a central agent in allowing some worms to live longer. The researchers argue that cytosolic catalase allows longer life by performing a function it wasalready known to serve: blocking cell damage caused by oxygen compounds. Such oxidative damage - analogous to metal rusting - has been implicated in human aging and diseases like AD, Lou Gehrig's and Parkinson's. Vitamin E, an antioxidant, is now used to prevent heart attacks and treat AD in some patients. The discovery of the catalase gene bolsters the theory that oxidative damage is central to both aging and its diseases. The worm gene "should give impetus to people working on the human genes to try to look for things like this,'' the researchers said. It may eventually be possible to protect human nerve cells by boosting catalase with a drug. By Jeff Donn Associated Press Writer; report in Nature 399, 162-166 (1999) 5/13/99

Stanford Ethics Panel Rejects Genetic Testing for AD - Genetic testing for AD currently is not appropriate for most people, a Stanford biomedical ethics group has concluded after studying the issue for nearly two years. Scientific understanding of the genetics of AD is advancing rapidly, and commercial tests are now available for some genes that have been associated with the disease. In most cases, however, these tests do not provide enough information to be useful except in research, according to a working group (http://www.stanford.edu/dept/scbe/alz.htm ) assembled by Stanford's Program in Genomics, Ethics and Society (PGES). The group presented the full version of its policy recommendations, along with 17 background papers, in a special issue of the journal Genetic Testing released last week (subscription info and publisher http://www.liebertpub.com/gte/default1.htm ). Either predictive or diagnostic genetic testing may be appropriate for individuals from families with a clear pattern of inherited, early-onset AD, the PGES working group concluded. But this disease pattern accounts for only a small percentage of AD cases. The PGES working group recommended that genetic testing not be used to aid diagnosis of the sporadic form of AD. The test improves the accuracy of diagnosis only slightly, and a positive result does not change prognosis or treatment for the patient. But for family members, who could learn of their own potential susceptibility from a relative's test, the results can impose psychological burdens and social costs even if good genetic counseling is available, the working group argued. PR 6/2/99

Caregivers
Medicaid Bears Much of AD Costs - Medicaid pays for much of the high cost of caring for Americans with AD, researchers conclude from their study of the Pennsylvania Medicaid program. "(When) family financial resources are exhausted, it is Medicaid rather than Medicare that bear's the lion's share of public expenditures for (AD-related) nursing home services," said study lead author Dr. Joseph Menzin. His team examined 1995 data on Pennsylvania Medicaid expenditures for all recipients over 50 years of age. They found that close to one in ten (8.4%) of these recipients had been diagnosed with AD and related types of dementia. Medicaid payments were about $8,200 higher on average for AD patients than for Medicaid recipients without the illness. They add that 96% of the cost difference between the group of patients with AD and the group who did not have AD was accounted for by nursing home expenditures. Menzin explained in a statement that "over the course of one year, recipients with AD and other types of dementia spent 228 days in nursing homes, on average, versus 120 days for a comparison group without these conditions." The team suggests that "given the anticipated growth in the elderly population, state officials may have an interest in alternative medical interventions to improve the care of AD in the community." Some of these alternatives to nursing home care include at-home case management, improved caregiver support and new drug therapies that may slow the progression of this debilitating disease. Reuters 4/19/99

For Elderly Who Want Independence, 'Assisted Living' Can Fill a Gap - Five years ago, Massachusetts had fewer than a dozen assisted-living centers. Today it has 115 and more on the way as national chains and local hospitals compete for a piece of the market. The desired demographics for a facility are lots of people over 75 with incomes of more than $25,000 a year, and just as important, many people with incomes of more than $75,000, to help pay for assisted living for their parents. Indeed, one criticism of assisted living is that Medicaid and Medicare, the federal insurance programs, do not cover it, so it is limited to the affluent. Market research tells developers that they have two customers: the older people who need a home that includes help, and their affluent children. Although some assisted living facilities purposely appeals to frailer people who might otherwise look at nursing homes, some facilities try to attract the healthiest people they can, in part because they cost less to care for. Extra services may be available as they are needed, but perhaps at a cost some residents can not afford. If a person requires long-term nursing care around the clock, many states prohibit the use of assisted living facilities. By Sara Rimer New York Times 5/9/99

Testing
Arcturus' PixCell a Finalist for Technological Innovation Award in Medical Diagnostics - Arcturus Engineering, Inc.'s PixCell™ Laser Capture Microdissection (LCM) system as a finalist in the 1999 Discover Magazine Award for Technological Innovation. The PixCell II™ LCM system was developed by Arcturus in collaboration with the National Institutes of Health. It is used in the research, prognosis and diagnosis of cancer, multiple sclerosis, arteriosclerosis, AD, AIDS, hepatitis, and fetal cell analysis. The system permits precision molecular analysis of a single cell or group of cells from solid tissue samples or cytological smears, providing critical infor- mation regarding the molecular and cellular basis of diseases. Dr. Robert Bonner of the NIH stated "When coupled with PCR and other exquisitely sensitive tools, LCM allows us to examine the complex molecular fingerprint of early stages of cancer (and other diseases) soon leading, we hope, to better prevention, diagnosis, and treatment." According to Dr. Lance Liotta of the NIH, "This technique allows us to study the disease while it is in progress -- and that is really powerful information to have in designing strategies to halt the disease process. Molecular analysis of pure cell populations in their native tissue environment is a critical element of the upcoming revolution in medical genetics and proteomics." See the NIH web site http://dir.nichd.nih.gov/lcm/LCM_Werbsite_Introduction.htm for more on this technique (yes "werbsite" is misspelled). PR 5/11/99

Nymox Corporation Announces Year-end Results - Revenues for 1998 increased to U.S. $257,508 from U.S. $65,943 in 1997, due in part to higher interest revenue and to increased sales. More than 50%, or U.S. $61,800, of the sales revenue for 1998 was generated in the fourth quarter when the AD7C™ urine test became available. Nymox currently markets the AD7C™ test as an aid to physicians in the diagnosis and management of AD. The Nymox AD7C™ test is the only test proven in multiple, double-blind coded clinical trials with independent physicians to be accurate and consistently useful. PR 5/14/99

Prevention
Eat Prunes, Raisins, and Berries to Help Prevent AD - Want to prevent AD? Then eat more prunes, raisins, blueberries, and blackberries, a new study shows. These foods were recently rated highest in antioxidant nutrients in tests by researchers at the Jean Mayer Nutrition Research Center on Aging at Tufts University in Boston. Many studies have shown that antioxidant nutrients -- which include vitamins C, E, and the vitamin A family of carotenoids, plus several minerals, notably selenium -- help prevent the brain cell damage that causes AD. They do it by neutralizing highly reactive oxygen molecules called free radicals. Here is the Tufts antioxidant "hit parade," measured "oxygen radical absorbance capacity," or ORAC units: Prunes, 5,770 ORAC units per 100 grams; Raisins, 2,830; Blueberries, 2,400; Blackberries, 2,036; Kale, 1,770; Strawberries, 1,540; Spinach, 1,260; Raspberries, 1,220; Brussels sprouts, 980; Plums, 949; Alfalfa sprouts, 930; Broccoli florets, 890; Beets, 840; Oranges, 750; Red grapes, 739; Red peppers, 710; and Cherries, 670. All these fruits and vegetables are richly colored: red, purple, blue, orange, or deep green. This is no coincidence: The antioxidants in these foods are most concentrated in the pigments that give them their color. Alzheimers.com 5/29/99

Other Items
False Recall in Older Adults and AD Linked to Attention, Not Memory, Breakdown - In an address 6/5 before the American Psychological Society meeting David Balota, professor of psychology at Washington University reported on his study which provides further compelling evidence in support of a relatively novel approach to understanding how AD cripples the human mind. The findings suggest that the cognitive problems associated with AD might be better conceptualized as a breakdown in attention rather than primarily a breakdown in memory in the classical sense. The results are quite consistent with recent neuropathological evidence linking AD to physical breakdowns in the frontal lobes, where much of the mind's strategic information processing, including attention functions, are believed to be in part coordinated. Taken together, these studies provide evidence for an attention-based model of AD. The findings demonstrate that older people are very susceptible to the creation of false memories which Balota finds interesting because it suggests that memory problems associated with aging are not the result of a broad general decline in all memory-related functions, but are due to sharp declines in some cognitive areas, specifically portions of the brain that control the strategic processing of information once it is recalled from memory. The notion now being put forth by Balota and other AD researchers is that the underlying structure of the knowledge-based memory system remains relatively intact, at least during early stages of AD, while critical strategic information processing systems in the brain's frontal lobe begin to break down. The loss of these strategic information processing skills, such as the ability to maintain attention on the memory task at hand, makes it increasingly difficult for the brain to accurately process and assimilate the information it initially set out to retrieve. The increase in false memory susceptibility among healthy older adults and individuals with AD seems to indicate that the mind is somehow overwhelmed by the flood of jumbled recollections still pouring in from an active network of knowledge-based associations. False memories result not from a lack of information, but from the mind's diminished ability to process the information and reach sound conclusions. If there is a better understanding of the manner in which such false memories are produced, maybe these individuals could be trained to avoid such distortions of memory. The critical first step is to determine which systems breakdown and which systems are relatively preserved in these populations. PR 6/4/99

Kodak Professional President Lauds Both Photos and Photographers In United Nations International Photographic Council Speech - Four photographers were honored for their work. Patrick T. Siewert, president, Kodak Professional, had high praise for Washington Post photographer and White House News Photographers Association photographer of the year Nancy Andrews. Urging his listeners to view Andrews' work on the Washington Post web site, http://www.washingtonpost.com/wp-srv/photo/partial_view/front.htm Siewert said, "Above all, do not miss her photo essay on Cary Henderson, a history professor with AD. These powerful pictures are greatly enhanced by captions -- fragments Nancy transcribed from audio tapes Professor Henderson recorded as his illness progressed. 'Affliction' is too gentle a word for the torment she uncovers," he said. "Nancy has received more than 75 awards for her work. But the real rewards are ours." PR 5/10/99

Americans Fear Living to 100 - As medical breakthroughs show promise in slowing the debilitating effects of aging, almost two thirds of Americans say they do not want to live to be 100, according to the results of a survey released by the American Association of Retired Persons (AARP). Survey respondents cited poor health and financial insecurity as the primary concerns about living to a very old age. They also expressed fear about losing mental faculties, depending on others, burdening their family, becoming isolated, and living in a nursing home. Most of those surveyed believed that there will be a cure for cancer, AIDS, AD and heart disease, the leading causes of death, in the next century. Reuters 6/3/99