Alzheimer Related News Items

*Acetylcholinesterase inhibitor
New Treatment for AD Licensed by Arena Pharmaceuticals - The product is an acetylcholinesterase enzyme inhibitor designated T-82. It has been extensively studied in animal memory and safety models and found to have a superior safety/efficacy profile when compared with other AD drugs such as Cognex and Aricept. Arena plans to file an IND to begin clinical development for T-82 later this year and initial efficacy studies in AD patients are scheduled for 1999. PR 4/14/98

Donepezil and Metrifonate Effective in AD Patients - Several studies on two new drugs were presented at the American Academy of Neurology annual meeting. A study showed donepezil (Aricept) improves behavioral symptoms such as apathy, hallucinations and purposeless, repetitive movements in addition to cognitive symptoms, for which it was approved. The study of 40 AD patients also show a significant reduction is the stress levels of patient's caregivers. To date more than 400,000 people in the US have begun Aricept therapy, a total of 55 million patient days. A 26-week study of 1,218 people with mild to moderate AD found that metrifonate (which has not been approved for use for AD) significantly improves patients' ability to perform basic daily activities such as dressing and eating as well as other activities such as making a phone call and doing housework when compared to patients who were given a placebo. 4/29/98

Pfizer on Aricept Performance - Aricept is a reversible actylcholinesterase inhibitor for mild to moderate AD. Total worldwide trade sales of Aricept totaled $78 million in the first quarter of 1998. Aricept accounts for about 97% of all AD prescription drug sales in the U.S. and has increased the number of US total prescriptions in this category roughly five fold. Aricept is receiving about two thirds of new prescriptions in Switzerland, where it was launched subsequent to Exelon's introduction. PR 4/14/98

*Nerve regeneration/protection
Guilford Pharmaceuticals Reports - A preclinical lead candidate has been selected in the
FKBP-neuroimmunophilin program with Amgen, which is undergoing additional preclinical research. FKBP-neuroimmunophilin ligands are a novel class of small molecules orally active neurotropic agents which are being developed to promote nerve regeneration and repair in neurodegenerative disorders. Amgen has been granted rights to ten specific indications including AD. PR 4/22/98

Neurobiological Technologies Forms Memantine Collaboration and Marketing Alliance with Merz & Co. GmbH - The purpose is to further the development and commercialization of Memantine, an orally-available neuroprotective agent. Merz, a German pharmaceutical company, has marketed Memantine in German since 1989 as a treatment for dementia. Merz is currently conducting a series of advanced clinical trials for dementia and AD. Memantine acts to modulate the N-methyl-D-aspartate (NMDA) receptor in the central nervous system. Modulating the NMDA receptor may protect against the neuronal injury associated with a number of neurological conditions, including dementia, AD and neuropathic pain. There are no currently neuroprotective treatments approved for any of the pathologies associates with NMDA-receptor overstimulation. PR 4/16/8

NeoTherapeutics Statement - Their technical platform regarding clinical and pre-clinical testing of their lead compound, AIT-082 (Neotrophin) is proceeding at an accelerating pace and they are pleased with Phase I clinical results to date. They have completed three Phase I single-dose human clinical trials, including two in Canada, in AD patients and one in the US under the auspices of the AD Cooperative Study. Plans are being completed to initiate a Phase II efficacy study in AD patients in early summer 1998. They are dedicated to the discovery and development of drugs that act on the central nervous system to repair nerve cells and treat neurodegenerative diseases and condition such as AD and others. PR 4/8/1998

NeoTherapeutics Annonces Research Program with AIT-082 - Report given that AIT-082 enhances memory function in both young adult and aged mice within two hours after oral administration. Further, prophylactic treatment with AIT-082 prevented or delayed the onset of age-induced memory deficits in mice when administered in the drinking water. When memory impairment was produced by specific brain lesions, AIT-082 restored memory performance and increase the genetic expression of neurotrophin-3 (NT-3), a natural protein growth factor associated withe nerve cell function. In Phase I clinical trials with AD patients, no serious side effects were observed. AIT-082 is quite different in mechanism than other AD drugs --it appears to enhance the latent capability of the nervous system to protect nerve cells, to resist damage and to stimulate the intrinsic repair mechanisms in the brain. PR 4/16/98

*Non-steroidal anti-inflammatory
Advil Donates $100,000 to Help in the Fight Against AD - In thanking them Alzheimer's Assn President and CEO Edward Truschke noted there is extraordinary progress being made in AD research today. Recent discoveries suggest we may soon find ways to more effectively treat the disease, slow its progression, and delay its onset, possibly someday preventing AD. Research shows that one in 10 persons over age 65 and nearly one-half over 85 have AD. Breakthroughs are being made, including preliminary research that suggests that non-steroidal anti-inflammatory drugs (e.g. ibuprofin, etc), vitamin E and estrogen may play a role in reducing the risk or slowing the progression of the disease. Introduced in 1984, Advil is the number one over-the-counter ibuprofen analgesic in the U.S.

*COX2 enzyme inhibitor
Merck Testing New Anti-inflammation Drug Vioxx - In a report to shareholders the president of Merck said they have high hopes for Vioxx, an osteoarthritis and pain drug what works by a new mechanism of action than existing compounds. The drug works by inhibiting an enzyme (cyclooxygenase-2), the so-call Cox-2 enzyme, that is responsible for producing pain and inflammation without affecting cyclooygenase-1 (COX-1), an enzyme that primarily protects the stomach lining. The undesired inhibition of COX-1 is believed to be the cause of serious GI side effects, such as stomach perforations, ulcers and bleeds. These side effects have been associated with the use of NSAIDs, or non-steroidal anti-inflammatory drugs. Merck will submit a new drug application for Vioxx in late 1988 and was conducting other trial to determine is effectiveness in preventing AD and colon polyps that can often lead to cancer. Reuters 4/29/98

*Aggression treatment
Unimed Announces 100% Revenue Increase for First-Quarter 1998 - For the growing number of AD patients, Unimed in investigating the use of Martinol to reduce aggression and resistiveness common to the disease. The drug may help caregivers better manage those with the disease and potentially allow them to stay in the home longer. The company is also developing faster acting formulations for Marinol. PR 4/21/98

*Herbal
FDA Rules to Restrict Herbal Remedy Claims - The FDA on 4/24/98 took the long awaited
action aimed at protecting consumers from misleading health claims by the booming herbal remedy industry. The new rules would bar makers of vitamins and herbal remedies from claiming to cure, prevent or alleviate cancer, AIDS or other specifics diseases. Instead, the products would be limited to making more general claims about enhancing the immune system, memory or other bodily processes. Washington Post 4/25/98 A01

Some Herbal Remedy Claims Unproven - Gingko biloba is among the herbs receiving superstar status in the pantheon of natural remedies purported to combat aging. Unfortunately, there is little evidence that ginkgo will sharpen you abilities if you are already healthy or if you are experiencing normal complaints of memory loss associated with aging. There is some promising evidence that it may improve cognitive functions in elderly people with dementia, but even so this herb is not the proverbial fountain of youth. Since ginkgo is a plant extract and is not regulated by the FDA, the active ingredients of different brands of ginkgo may differ substantially. AP (Dr. Barry Reisberg) 5/6/98

*Memory enhancement
Cortex Pharmaceuticals Announces Two Ampakine Patents - One of the patents covers
Ampalex (CX516) which is currently in clinical trials for treatment of AD and schizophrenia. Nerve cells communicate with each other by releasing messenger molecules called neurotransmitters. The most widely utilized neurotransmitter in the brain is glutamate. Ampakines work by increasing the effect of glutamate on one of its important receptors, the AMPA neuroreceptor. Cortex has found that increasing the effect of glutamate with a pharmaceutical compound could have beneficial effects, including improved memory. PR 5/5/98

*Anti-cortisol
Study Supports Role of Anticort In Treating AD, HIV - Anticort, the world's first drug designed expressly to reduce elevated levels of the stress hormone cortisol, may be effective in treating AD, other age-related diseases and AIDS. Anticort is an anti-cortisol (steroidogenesis inhibitor) drug that prevents and treats deadly immunosuppressive effects of elevated cortisol. Anticort's effectiveness in the treatment of AD is promising. The drug reduces both cortisol and cholinesterase --an enzyme responsible for destroying the key neurotransmitter acetylcholine. The study serves as a strong catalyst to begin testing Anticort for the treatment of AD patients. The maker, Steroidogenesis Inhibitors International, is planning to begin such tests later this year.   Nature Neuroscience (1998;1(1):3-4, 69-73) [NOTE: This is a new journal --free full web access until 5/31/98 http://neurosci.nature.com/]

*Other drugs
Japan Yet to Rule on Brain Drugs - The Health Ministry will reach a conclusion later this
year on the efficacy of several drugs marketed by firms in Japan for the treatment of brain-related diseases such as AD. The drugs are know as cerebral metabolism improvers and are often used to treat senility and dementia, including AD. The drugs include Takeda Chemical Industries' Avan, Yamanouchi Pharmacetuical's Elen, Fujisawa Pharamaceutical's Alnert, Tanabe Seiyaku's Sermion and Hoechst Marion Roussel's Hextol. Reuters 4/20/98

American Biogenetic Sciences Inc. Forms Agreement with Trevigen - Trevigen is developing screening assays for the detection of apoptosis, or programmed cell death which plays a role in certain neurodegenerative disorders (such as AD and Parkinson's disease) and has agreed to evaluate ABS' neurological compounds [monoclonal antibodies (Mabs) utilizing the ABS' patented Antigen Free technology] in this screening assay. PR 4/13/98

Elan to Acquire Neurex - The combined company is said to be well positioned through a series of strengths including leading research programs in AD, cell trafficking and in neuronal calcium channel blockers. PR 4/29/98

SIBIA Neurosciences Reports Financial Results - Expenses included continued pre-clinical development of SIB-1553A currently in development for AD. PR 5/1/98

Neurocrine Completes Enrollment in Phase III Clinical Trial for AD - The double-blind placebo-controlled clinical trials are with a neurosteroid compound for AD. Results from the trial are expected to be announced at year end. PR 5/4/98

Forest Laboratories Reports - They have a product LU-25-109, a selective muscarinic agonist for AD, which is presently in Phase II/III clinical trials. PR 5/5/98

Genes & Genetic Issues
Gene Tied to Rare Form of Parkinson's Disease - Mutations in a gene on chromosome 6
results in juvenile parkinsonism. The gene makes a protein they named "parkin" and this protein is considered responsible for the development of the disease. This newly discovered protein is similar to proteins implicated in other neurodegenerative diseases like AD. Nature (1998;392:544-545, 605-608)

Caregivers
New Test Predicts Crash Risk of Older Drivers - A new vision test (a novel "useful field of view" test) may ultimately help the elderly, their families and physicians decide when it's okay for an older person to continue driving or when it may be time to hang up the car keys. Poor performance on the test was linked to an increased risk of car crashes. [The study does not relate to AD]. JAMA 4/8/98

Condition of Spouse Affects Timing of Decision to Enter Hospice Care - The health status of a spouse plays an important role in determining when a terminal patient seeks hospice care. Compared to patients with the healthiest spouses, those with moderately sick and very sick spouses has considerably later enrollment into hospice, with the median survival decreasing from 111 to 49 to 22 days across the groups. The study was supported by a grant from the Alzheimer's Assn. Journal of Palliative Medicine 4/23/98

Rocking Helps Elder Depression - Study shows extended periods of rocking in rocking chairs may provide relief from anxiety and depression for nursing home residents suffering from dementia. The more elders rocked, the more their symptoms of anxiety, such as crying or tension, and depression decreased. In addition, the elders who rocked the most requested less pain medication. Presentation at Eastern Nursing Research Society 4/25/98

Study Finds Best Drugs for Depression in the Elderly - Only two families of drugs seemed to be effective - heterocyclic drugs such as imipramine, nortriptyline, and doxepin; and selective serotonin reuptake inhibitors such as fluoxetine. Archives of Internal Medicine (1998) 158:705-712

Report Shows Nation Ill-Prepared to Meet End-of-Life Needs of Older Women - The Alliance for Aging Research issued a report drawing upon more than 50 current studies and surveys and concludes that American women are more likely than men to be sicker, poorer, alone, and with the greater care needs at the end of their lives. Women live longer than men, and they are more likely to suffer from chronic conditions such as arthritis, osteoporosis and related fractures, AD and incontinence.

Testing
Alzheimer's Association Announces Winner of Hatfield Research Award - They grant their
annual Senator Mark Hatfield Award for Clinical Research in AD to Michelle Papka, Ph.D. for a project to improve the diagnosis of the Lewy Body variant (LBV) of AD. The LBV of AD has been estimated to account for 20% of age-related dementia, however clinical diagnosis of this disease remains a challenge. The research will determine if neuropsychological testing can distinguish between the two disease types and lean if the groups differ with respect to genetics and markers in cerebrospinal fluid. The Alzheimer Assn. said there is a strong evidence that brain degeneration associated with AD may begin up to 40 years before the first clinical symptoms appear. Early detection tools are needed for diagnosis of presymptomatic cases and to enable us to better track the progression of the disease and evaluate drugs in clinical trials. PR 3/20/98

World Panel Outlines Tests for AD - The panel said: (1) For early-onset AD these mutations are relatively rare and testing should be limited to those with a family history of early-onset AD. (2) For late-onset and sporadic AD, a check for certain mutation of the APOE gene, known as APOE4, can help a diagnosis made on the basis of psychiatric tests. It should not be used as the only test. (3) The APOE4 test is not appropriate for people who have no symptoms of AD. No other test were truly appropriate, the panel decided. "These include amyloid deposits in skin (skin test), pupil dilation in response to dilute solution of tropicamide (eye-drop test), neuronal thread proteins in cerebrospinal fluid (AD7C) and serum levels of iron binding protein p97," the Alzheimer Association said. Reuters 4/7/1998

Nymox Pharmaceutical Corp. Announces Independent Clinical Study Verification of its AD7C-NTP Alzheimer Testing Technology - Nymox announced that an independent multicenter follow-up study of dementia patients has verified the accuracy of the Nymox AD7C-NTP test as an aid to physicians in the diagnosis of AD. The results will be presented at the American Geriatrics Society meeting in May and are expected to be published at a later time. PR 4/7/1998

Prevention
Estrogen Reduces Risk of Parkinson's Dementia - Women with Parkinson's disease who
also take estrogen replacement therapy may significantly reduce their risk of developing the dementia often associated with the disease. Since estrogen has been shown to have a protective effect against AD, the findings indicate that, at least in a subset of patients, Parkinson's disease dementia may in fact be coincident AD. Neurology (1998;50:1141-1143)

Exercise Protects Against AD - Decades of routine recreational exercise appears to protect against AD. Non-exercisers are more than three times as likely to develop AD in later life as people who add exercise to their leisure activities between ages 20 and 29. Dr. Friedland said that even though the study involved exercise activities early in life, "it is never too late to begin exercise as long as one is in good physical health. I think exercise should help protect against AD." The point is exercise does a lot of things hormonally and biochemically for you and it may be good for your brain as well as your heart. Annual Mtg. Am. Acad. of Neurology 5/1/98

High Blood Pressure Again Linked to Memory Loss - Several studies have linked mid-life high blood pressure to late-life dementia. A new study show that treating high blood pressure early may prevent learning and memory trouble later. Researchers warn that it remains unclear whether hypertension causes cognitive impairment. But the findings emphasize the importance of testing for and treating high blood pressure in the elderly. Hypertension (1998) 31:780-786

Illiteracy, Alzheimer's Linked - Researchers found that 20% of Israeli Arabs over the age of 60 suffer from AD. Almost half the men and 95% of the women in that group had no schooling. In the largest village of Israeli Arabs in Israel, Wadi-Ara, there were 823 people over the age of 60 who took part in the study. The study confirms that education protects people against developing AD. And because the study included almost every elderly person in Wadi-Ar, it is free from educational bias attributed to previous work in the field. UPI 4/29/98

Study: Smoking by Elderly May Contribute to Mental Decline - Elderly smokes may lose the ability to think, perceive and remember more quickly than people who never smoked or who quit smoking according to a new study. This is not an AD story. American Academy of Neurology Annual Meeting 4/30/98

The Wellness Councils of America Addresses Treatment Options for Women at Menopause - Their booklet  "What's Right For Me" is available free to women (call 800-561-2781) and provides evidence-based information about the variety of options available at menopause and is designed to help women make informed health care decisions at midlife. It provides information on the short-term symptoms of menopause such as hot flashes, night sweats and vaginal dryness, as well as how the loss of estrogen in the body can lead to increased risk of heart disease, osteoporosis, and possibly AD. PR 6/6/98

Research Facilities
Praecis Pharmaceuticals Announces Formation of Provid Research Division in New Jersey - This new division for chemistry research and development will enable evolution of leads discovered by gene- and peptide-based lead discovery into small molecule drug candidates through the methodologies of peptide mimetics, medicinal chemistry, molecular modeling, and computational chemistry. The Provid Research division will be located in New Jersey near Rutgers University. Praecis is developing an amyloid aggregation inhibitor for the treatment of AD. PR 4/7/1998

Novartis Announces Formation of the Novartis Institute for Functional Genomics - To date, hundreds of links have been made between generic characteristics and many of today's major diseases, such as AD, diabetes, asthma, depression and cancer. However, to derive a therapeutic benefit, more needs to be learned about the functional relationship between a particular genotype and a disease state. Functional genomics encompasses all of the activities and techniques involved in clarifying this relationship. Funding will be $250 million. PR 4/8/1998

Cornell Gets $100 Million from Weil - The head of the Travelers Group has given Cornell University a $100 million endowment to the medical college and graduate school of medical sciences. The money will be used to strengthen research in three areas: structural biology, genetic medicine and neuroscience. AP 5/1/98

NeuroLab
Scanalytics' IPLab Image Processing Software for Neurolab Mission - This study is designed to determine whether the sensory information provided by gravity after birth is necessary for the development of spatial ability. Researchers will quantitate neuronal patterns in developing rat brains following sixteen days in space. The medical application of this study could affect a variety of patients suffering from AD, muscular dystrophy and stroke. These are all brain afflictions in which spatial ability is impaired. PR 4/14/98

Crew Packs in Rat Studies - The point of the rat experiments is to look for structural changes in neural passageways due to the exposure to microgravity. The research also is expected to help explain why those areas in human brains sometimes fall apart, such as in AD patients. UPI 4/24/98

Shuttle Rats in AD Research - With microscopic wires protruding from their brains, four rats aboard the shuttle Columbia are scrambling around surrealistic looking mazes in an experiment that could help unravel how AD numbs memory and reasoning. The same region of the brain that generates mental maps is also the gateway to long-term memory in humans and is the part of the brain that fails in normal aging and in AD. Researchers will be able to discern exactly how specific neurons in the rats brain are responding during the experiment, which tests how well the subjects can orient themselves in the mazes. Understanding the basic biology of the highest level of the association cortex in the brain will give an understanding so researchers can tell what is going wrong. This knowledge is a critical prerequisite to any kind of interventions that would be helpful in AD. UPI and Reuters 4/20/98

Other Items
Extra Choline During Pregnancy Enhances Memory in Offspring - Pregnant rats fed extra
doses of an essential nutrient, choline, produced offspring whose brain circuits were "wired" to learn and remember far more efficiently than offspring without the supplement. This common food nutrient has been shown to cause permanent brain changes in regions responsible for learning and memory. Choline is a naturally occurring amino acid found in egg yokes, milk, nuts, liver and other meats as well as in human breast milk. It is the essential building block for a memory-forming brain chemical called acetylcholine, and it plays a vital role in the formation of cell membranes throughout the body. Neurophysiology 4/98

Sudden Cognitive Decline Is Not Part of Normal Aging - By testing older adults repeatedly for up to 15 years, researchers have shown that a sudden decline in mental ability is not a normal part of aging, but can signal the onset of AD. When such an illness attacks, there is a deterioration in cognitive performance that often is detectable over a relatively short period of time. People without the disease can look forward to good mental function in old age. Unfortunately those with AD usually face a sharp decline. Archives of Neurology (55:395-401 March 1998)

Alzheimer-Cancer Link Possible - The dramatic cell loss in dementia is believed to be caused a death process which is initiated by cells trying to divide as the neurons in the adult brain are trying to go through the cell-cycle again. Study determined neurons in AD patient's brain produce proteins that trigger cell division. Aberrant expression of cyclin D, cdlk4, proliferating cell antigen and cycline B1 were found in AD brains, but not any of these cell cycle markers were found in the controls with no AD. The cancer link is that in both diseases there is a loss of cell cycle control. What happens in cancer is that the cells begin to divide, but they go through the cell cycle in an uncontrolled way. Journal of Neuroscience 4/15/98

Research links Low Levels of Fluoride and Aluminum to AD and Kidney Damage - The presence of low levels of fluoride in the drinking water of test animals, equal to the amount of elemental fluorine found in fluoridated water, caused damage to tissue of the brain that the authors identified as similar to the pathological changes found in humans with AD and other forms of dementia. The authors summarize, "Chronic administration of aluminum-fluoride and sodium-fluoride in the drinking water of rats resulted in distinct morphological alterations of the brain, including the effects on neurons and cerebrovasculature." Journal of Brain Research vol. 784, 1998

Value of Animals, Plants and Microbes to Human Health - Seminar - The fugu pufferfish produces tetrodoxin, a poison that is "exquisitely" targeted against sodium channels. Tetrodoxin acts to prop open the sodium channels on the surface of the cell letting too much sodium into the cells and destroying them. Tiny Amazon frogs also produce a poison, betrachotoxin, but over millions of years the frog has become insensitive to its effect. If scientists could figure out just what the modifications are that the frog has made, they could possibly use the same mechanism to treat human diseases in which sodium can destroy cells such as AD and Parkinson's, both fatal and incurable brain diseases. Reuters 5/4/98

Ron Reagan on his Famous Dad - In an interview he said as to the state of his father's health "All things considered, he is holding his own. But he's not young anymore and he's had this disease (Alzheimer's) for quite some time now." UPI 4/16/98

Diagnon Corp. Receives Research Grant - They will study the brains , behavior and health of the great apes - mankind's closest relatives. The apes will be observed, videographed and when possible given memory tests. When the apes die of natural causes their brains will be retrieved at autopsy and will undergo detailed neurological exam with the same methods used to study the brains of human victim of neurological disorders. The project aims to increase the understanding of normal aging processes and to assist in improving methods of diagnosis, prevention, treatment, and management of age-related neurodegenerative disorders such as AD.
PR 5/5/98