The editors of The Journal of Allergy and Clinical Immunology are pleased to announce the July issue, highlighting AIDS and AIDS research. The Journal of Allergy and Clinical Immunology (http://www.jacionline.org/) is the official journal of the American Academy of Allergy and Clinical Immunology, and is published by Elsevier.

The issue coincides with the XVII International AIDS Conference, taking place at Centro Banamex, Mexico City, August 3 to 8, 2008. Donald M. Leung, Editor-in-Chief said, “AIDS is a topic of global importance and we believe that this collection of articles, written by some of the leading figures in HIV and AIDS research, will be of great interest to the many researchers and clinicians gathering in Mexico City.”

Key papers include a review article by Barton F. Haynes from Duke University and Robin J. Shattock from St. George’s University of London that summarizes some of the hurdles that researchers face in developing an HIV vaccine. Additionally, a mechanistic review by Susan Moir and Anthony S. Fauci from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases looks specifically at B-cell abnormalities associated with HIV, in the hopes that - as the authors state in their article - “A better understanding of the pathogenic mechanisms of B-cell abnormalities […] can potentially lead to new strategies for improving antibody responses.”

Also, a Rostrum article by Lin Shen and Robert F. Siliciano from Johns Hopkins University argues that highly active antiretroviral therapy (HAART) must be combined with new techniques to attack the viral reservoirs that remain even after viral replication has been stopped.

Other issue highlights include original research from a National Institutes of Health multi-center group that finds an increased rate of asthma in HIV-infected children who are being treated with HAART; the report of genetic variations in the innate immune mannose lectin-binding pathway that changes the rate of HIV disease progression; and the laboratory advancement of measuring na?ve and late activated cytotoxic T lymphocytes as a simpler method of measuring thymic function.

Subscribers can access the full content of each issue of The Journal of Allergy and Clinical Immunology at the journal web site, http://www.jacionline.org/. Institutional subscribers can access the journal through ScienceDirect, http://www.sciencedirect.com/science/journal/00916749.

Visitors to the XVII International AIDS Conference in Mexico City are encouraged to stop by the Elsevier display (Booth #503) to see the special AIDS issue and to learn how to subscribe to The Journal of Allergy and Clinical Immunology subscriber.

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About The Journal of Allergy and Clinical Immunology

The Journal of Allergy and Clinical Immunology, the official publication of the American Academy of Allergy, Asthma, and Immunology (AAAAI), provides timely clinical papers, cutting-edge research, and comprehensive reviews in the fields of allergic disease and clinical immunology. The Editor-in-Chief is Donald YM Leung, MD, PhD. More information about the journal can be found online at http://www.jacionline.org/.

About Elsevier

Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier’s 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect (http://www.sciencedirect.com/), MD Consult (http://www.mdconsult.com/), Scopus (http://www.info.scopus.com/), bibliographic databases, and online reference works.

Elsevier (http://www.elsevier.com/) is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc (http://www.reedelsevier.com/), a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier’s ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

Source: Caroline Foote
Elsevier

As the world’s attention turns to the global HIV/AIDS epidemic with the convening of the International AIDS Conference in Mexico City, the U.S. Centers for Disease Control and Prevention (CDC) is anticipated to announce on August 3rd significantly higher HIV incidence numbers for the United States. Past estimates have been 40,000 new infections per year; the new number may be more than 25% higher. In reaction to the pending announcement Dr. Gene Copello, Executive Director of The AIDS Institute, issued the following statement:

“Let this serve as yet another wake-up call to our government leaders in Washington, D.C., the States and Territories. We cannot turn our backs on the HIV/AIDS epidemic in our own country. HIV/AIDS is devastating many communities, particularly gay men, African Americans, Latinos and injection drug users. The AIDS Institute calls upon President Bush, the Congress, together with both Presidential candidates, to support a National AIDS Strategy and to demonstrate their leadership by committing immediately to preventing HIV in the United States through increased funding for the CDC HIV Prevention programs, and the establishment and implementation of prevention policies and programs based on sound scientific evidence.

For next year, President Bush has proposed to cut the CDC HIV Prevention budget by $1 million. This is on top of this year’s budget cut of $3.5 million. Neither the U.S. House of Representatives nor the U.S. Senate has proposed any increased funding for HIV Prevention. This is completely unacceptable, particularly in light of the new incidence numbers. Congress must increase funding for HIV Prevention for next year by at least $30 million. This is far from what is needed, but it is, at least, a necessary first step.

The AIDS Institute calls on the Administration, Congress, and the Presidential candidates to support policies and programs that are scientifically known to prevent HIV prevention, such as comprehensive sex education, HIV testing and counseling, and syringe exchange. Further, we call upon our leaders to commit the resources necessary at the National Institutes of Health to conduct behavioral research and to continue to develop such biomedical prevention approaches as microbicides and a vaccine. The government also needs to end programs and policies that are proven not to work, such as abstinence-only-until-marriage programs.

With the revelation that there are more people being infected with HIV in the U.S. each year means more people will be identified as living with HIV/AIDS. It also means they will need adequate healthcare and lifesaving medications to keep them healthy. Again, we must turn to our government to make sure the necessary resources are there for them.

The United States has made a remarkable, and much needed, commitment to global AIDS through the recent reauthorization and expansion of the President’s Emergency Plan for AIDS Relief (PEPFAR). This demonstrated profound leadership on the part of our government. Addressing the HIV/AIDS epidemic at home in our own country requires the same leadership, action, and resolve by our leaders, and those aspiring to become our leaders. The clock is running out, there is no better time than right now to end AIDS in America.”

The AIDS Institute is a national nonprofit agency that promotes action for social change through public policy research, advocacy and education.

The AIDS Institute
http://www.theaidsinstitute.com

A new study suggests that those who are unmarried or not living with a partner in midlife could have an increased risk of developing Alzheimer’s disease, according to research reported today at the 2008 Alzheimer’s Association International Conference on Alzheimer’s Disease (ICAD 2008), in Chicago.

Additional research on Alzheimer risk factors presented at ICAD 2008 indicates that people who ruminate, or repeatedly think about their problems, may be less likely to develop the disease, while people with metabolic syndrome (a combination of cardiovascular health related symptoms) are at higher risk. Finally, a large meta-analysis of nine European risk factor surveys confirmed a well recognized group of Alzheimer risk factors, including memory complaint, severe head trauma, diabetes, stroke and low education.

“We may not be able to do anything about aging, genetics or family history, but research shows us that there are lifestyle decisions we all can make to keep our brains healthier as we age, and that also may lower our risk of developing Alzheimer’s disease,” said William Thies, PhD, vice president for Medical & Scientific Relations at the Alzheimer’s Association.

Unmarried Life: Paving the Way for Dementia?

Research suggests that maintaining regular social interaction can contribute to maintaining brain health as we age and possibly decrease one’s risk of developing Alzheimer’s. When people are married they are able to have close interaction on a regular basis. This may reduce the occurrence of dementia.

Krister Hakansson, BA, of Karolinska Institutet, KI Alzheimer Research Center, Stockholm, Sweden and Vaxjo University, School of Social Sciences, Vaxjo, Sweden, conducted a first-of-its-kind evaluation of whether midlife marital status is related to late-life cognitive function. The study examined 1,449 individuals from the Finnish Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study in midlife and then again in 1998, an average of 21 years later.

At re-examination, 139 persons were diagnosed with some form of cognitive impairment: 82 with mild cognitive impairment (MCI) and 48 with Alzheimer’s. Persons in the study who were living with a partner in midlife were significantly less likely to show cognitive impairment compared to all other categories (single, separated, divorced or widowed). Those in the study who were married or lived with a significant other in midlife had a 50% lower risk of having dementia in late-life compared to those who lived alone, even after adjustments for education, BMI, cholesterol, blood pressure, occupation, physical activity, smoking habits, depression, ApoE status, age at follow-up and gender.

The researcher observed that there were differences between groups of people who had been living alone for different reasons. The all-life singles had a doubled risk, whereas the ones who stayed divorced from midlife onwards had a tripled risk. The most dramatic risk increase was found for those widowed before midlife and who stayed widowed. Compared to those married at midlife and still so at late-life, they had more than a six-fold risk of developing Alzheimer’s.

“Living in a couple relationship is normally one of the most intense forms of social and intellectual stimulation. If social and cognitive challenges can protect against dementia, so should living in a couple relation,” said Hakansson. “This study points to the beneficial effects of a married life, consistent with the general hypothesis of social stimulation as a protective factor against dementia.”

Tendency for Rumination in Midlife May Decrease Risk for Dementia Decades Later

According to Ramit Ravona-Springer, MD, of Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel and colleagues, “rumination” refers to the disposition for repetitive thinking over one’s problems.

Tendency for rumination when confronting difficulties in family and work settings was assessed in about 9,000 participants in the IIHD study, a longitudinal investigation of the incidence and risk factors for cardiovascular disease among Jewish male civil servants in Israel. Tendency for rumination was assessed as 1=always forget, 2=tend to forget, 3=tend to ruminate, 4=usually ruminate.

Dementia was assessed three decades later in 1,890 participants among 2,604 survivors of the original cohort. Mean age of the participants was 82 at the time of final assessment. 308 were diagnosed as demented, 175 as having mild cognitive impairment, and 1,407 had no cognitive impairment.

The prevalence rates of dementia (adjusted for age, area of birth, and socioeconomic status) were 21% for those who always forget difficulties in familial settings, 18% for those who tend to forget, 14% for those who tend to ruminate over difficulties, and 14% for those who usually ruminate. When rumination in response to difficulties at work was assessed, prevalence rates of dementia were 24% for those who always forget difficulties, 19% for those who tend to forget, 15% for those who tend to ruminate over difficulties, and 15% for those who usually ruminate.

A total score for rumination in both family and work settings was calculated, and subjects were divided into four groups according to this score. Relative to the group with the lowest total rumination score, dementia prevalence was 30 to 40 percent less in groups with higher scores.

“Your personality traits, specifically your psychological and cognitive style when confronting distress, may be associated with your risk for dementia,” said Ravona-Springer. “However, exactly how this works still needs to be determined.”

Metabolic Syndrome May Lead to Cognitive Decline

Metabolic syndrome (Met.S) is a group of heart disease risk factors that includes abdominal obesity, elevated blood pressure, high triglycerides, elevated blood sugar and low HDL cholesterol. Those who have Met.S are at higher risk for developing diabetes, hypertension, and stroke, all of which increase the risk of developing dementia, including Alzheimer’s disease.

Matheus Roriz-Cruz, MD, PhD, Federal University of Rio Grande do Sul State, Brazil and colleagues studied the effects of Met.S on the development of cognitive impairment in people who have not had a stroke. Researchers evaluated 422 healthy elderly men and women over age 60 in Brazil and used a battery of scales to assess cognition, depression, planning and activities of daily living. Met.S was present in 39.3% of participants.

Data from the study revealed that all neurofunctional scores were significantly lower for those with Met.S, and the difference increased with age. Older people with Met.S had an almost 35% higher level of cognitive compromise when compared to those without Met.S.

“Met.S was independently associated with lower cognitive, planning, neuromotor and functional scores, and with more depressive symptoms,” said Roriz-Cruz. “The results from this study reinforce the importance of maintaining good physical health in order to reduce one’s risk of experiencing cognitive decline, and possibly developing Alzheimer’s disease.”

Risk Factors for Progression to Dementia in General Population

In the general population, many risk factors and predictors for dementia have been identified. However, a combination of risk factors may give a more accurate prediction for dementia than each individual risk factor.

Sylvaine Artero, of INSERM, Montpellier, France; Pieter Jelle Visser, of the University of Maastricht, The Netherlands; and colleagues analyzed a pooled database constructed from nine European surveys of dementia risk factors, including a total of 16,261 participants over age 55 without dementia. Potential risk factors were evaluated at baseline and incident dementia was assessed over a follow up period of up to 15 years. Risk factors included cardiovascular disorders, endocrine disorders, depression, head trauma, intoxicants (including alcohol, smoking and drugs), physical and intellectual activities, performance in activities of daily living, Apolipoprotein E genotype, cognitive complaint, and cognitive test performance.

In total, 1,530 subjects (9%) progressed towards dementia. In order, the most predictive variables were: impairment in executive function (planning), memory problems (as measured on tests), subjective complaints about memory/cognitive failure, Apolipoprotein E (ApoE) genotype, use of psychotropic medication, severe head trauma, diabetes, stroke, and problems with language. In addition, problems with activities of daily living, smoking, no drinking, no use of hypertensive drugs, low education, and female gender all independently predicted dementia at follow-up.

“Cases of dementia in the general population can be best identified by a combination of socio-demographic, clinical and cognitive factors,” said Artero. “Developing a better understanding of the factors that increase risk for Alzheimer’s will help us to create more effective methods to prevent people from developing the disease.”

About ICAD 2008

The 2008 Alzheimer’s Association International Conference on Alzheimer’s Disease (ICAD 2008) is the largest gathering of international leaders in Alzheimer research and care ever convened. At ICAD 2008, more than 5,000 researchers from 60 countries will share groundbreaking information and resources on the cause, diagnosis, treatment and prevention of Alzheimer’s and related disorders. As a part of the Association’s research program, ICAD serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community. ICAD 2008 will be held in Chicago at McCormick Place, Lake Side Center from July 26-31.

About the Alzheimer’s Association

The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s research, care and support. Our mission is to eliminate Alzheimer’s disease through the advancement of research, provide and enhance care and support for all affected, and reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. For more information, visit http://www.alz.org.

— Krister Hakansson - “Unmarried life: Paving the way for dementia?” (Funders: Gun and Bertil Stohne Foundation)

— Ramit Ravona-Springer - “Tendency for rumination as a psychological cognitive style in midlife is associated with decreased risk for dementia three decades later.” (Funders: Israel Science Foundation, Israel Academy of Sciences and Humanities)

— Matheus Roriz-Cruz - “Metabolic syndrome, successful and pathological neuroaging in a stroke-free elderly population.” (Funders: Ministries of Education, Brazil and Japan)

— Sylvaine Artero, Pieter Jelle Visser - “Risk factors for progression to dementia in general population: the Descripa study (European pooled data base).” (Funder: European Commission, 5th framework programme (QLK-6-CT-2002-02455))

Alzheimer’s Association
http://www.alz.org

Calypso Medical Technologies, Inc. (Calypso Medical) has announced that eight new abstracts will be presented on prostate motion management in radiation therapy using the Calypso® 4D Localization System (Calypso System) at the AAPM annual scientific meeting July 27-31, 2008 in Houston, Texas. These scientific abstracts summarize clinical experiences with the first commercial installations of the Calypso System in radiation therapy.

The Calypso System is the only product platform that provides real-time tumor tracking during radiation treatment. This information is critical in assuring the clinician and the patient that the radiation treatment prescribed is delivered to the cancerous tissue while avoiding adjacent healthy organs. Known as GPS for the Body®, the Calypso System utilizes implanted Beacon® electromagnetic transponders smaller than a grain of rice to enable continuous tracking of the prostate during radiation treatment.

“We are extremely pleased to have such rapid adoption of this technology in its first year and a half of commercialization. The Calypso System is being used in more than fifty leading cancer centers across the nation and more than 1,500 prostate cancer patients have benefited from this technology in a very short period of time. Patients are seeking out sites that offer GPS for the Body® technology. The patients we have talked with consider this technology to be a critical component of their treatment success,” says Eric R. Meier, CEO and President.

Calypso Medical will feature motion management solutions at Booth 100, including its most recent product upgrades for Beam On Reporting, Workflow Efficiency Enhancements and work-in-progress new system release for motion management; Adaptive Couch Repositioning and Motion Analysis Trend Reporting. The company will also highlight investigational pre-clinical studies underway for breast and lung cancer applications using the Calypso System.

Additionally, in May 2008 the U.S. Food and Drug Administration (FDA) cleared a new indication for the use of implantable Beacon® electromagnetic transponders for use in patients who have had a prostatectomy for follow-on external beam radiation therapy. Radiation therapy is the standard of care for patients with a high risk of prostate cancer recurrence or those in whom recurrence has been diagnosed. Studies indicate up to 40% of prostatectomy patients are diagnosed with recurrent prostate cancer following surgery and require radiation therapy.

The Calypso System will be highlighted in eight abstracts utilizing the technology to manage prostate motion on-line and off-line including an oral presentation by Dale W. Litzenberg, Ph.D. from the University of Michigan. The presented abstracts will be published in the [August 2008 Vol. 25, Issue 8] issue of the journal Medical Physics and include:

Predictability of Patient Specific Margins from Real-Time Intrafraction Motion Measurements
D. Litzenberg, et al, University of Michigan, Ann Arbor, Mich.
Wednesday, July 30, 4:00 p.m., Auditorium C

Analysis of Prostate Patient Setup Error and Organ Motion Error Using Calypso Setup Shift and Tracking Data
Z.Su, et al, Virginia Commonwealth University, Richmond, Va.
Sunday, July 27, 1:30 p.m., Exhibit Hall 3

Comparison of CBCT and Electromagnetic Transponders for Prostate Localization
J. Tanyi, et al, Oregon Health and Science University, Portland, Ore.
Sunday, July 27, 2:15 p.m., Exhibit Hall 3

The Accuracy and Stability of the Calypso System for Prostate Localization and Motion Tracking
J. Li, et al, Fox Chase Cancer Center, Philadelphia, Pa.
Sunday, July 27, 3:00 p.m., Exhibit Hall

Dosimetry Impact of Radiation Beams Due to Presence of Calypso Electromagnetic Array
S. Li, et al, University of Nebraska Medical Center, Omaha, Neb.
Sunday, July 27, 3:00 p.m., Exhibit Hall

Real Time Tracking of Inter Marker Distances to Assess Maker Stability, Organ Deformation in Prostate Cancer
A. Mahadevan, et al, Cleveland Clinic Foundation, Cleveland, Ohio
Sunday, July 27, 3:00 p.m., Exhibit Hall

Assessment of Conebeam CT Image Quality in the Presence of an Electromagnetic Tracking System
L. Santanam, et al, Washington University School of Medicine,
St. Louis, Mo.
Sunday, July 27, 3:00 p.m., Exhibit Hall

Geometric Uncertainty Caused by Prostate Rotation During Radiotherapy
L Jin, et al, Fox Chase Cancer Center, Philadelphia, Pa.
Sunday, July 27, 3:00 p.m., Exhibit Hall

About Calypso® Medical

Calypso Medical Technologies, Inc. (”Calypso”) is a Seattle, WA-based privately held medical device company. The Company’s proprietary tumor localization system utilizes miniaturized implanted devices (Beacon® electromagnetic transponders) to continuously, accurately, and objectively pinpoint the location of tumors for improved accuracy in radiation therapy. Calypso addresses two major issues in modern radiation oncology: errors in treatment set-up and tumor motion during treatment. In addition, the Calypso® 4D Localization System’s non-ionizing electromagnetic guidance has been found to improve work flow efficiency and treatment room utilization. The technology is designed for body-wide cancers commonly treated with radiation therapy, including prostate, breast, lung, head, neck and other radiation therapy target organs. The products are FDA 510(k) cleared for use in the prostate and prostatic bed. http://www.calypsomedical.com.

NYU Langone Medical Center researchers have long been making important contributions to the understanding of Alzheimer’s disease. They were among the first to characterize amyloid, the plaque-forming protein implicated in Alzheimer’s, and the first to describe a genetic mutation in a familial form of the disease. They also developed the first successful intervention program to reduce the need for placing patients in nursing homes and alleviate caregivers’ depression.

At the 2008 ICAD meeting, NYU Langone Medical Center researchers are presenting a wide range of findings from both clinical studies using state-of-the-art methods to discern the earliest sign of Alzheimer’s and from animal studies aimed at understanding how amyloid causes neuronal dysfunction in the brain. All of this research helps advance the understanding of Alzheimer’s, which now afflicts more than 5 million Americans. A better understanding, it is hoped, will lead to more effective therapies that will slow the progression of the disease and ultimately to ways to prevent its onset.

The following news tips are based on poster and oral presentations at the Alzheimer’s Association 2008 International Conference taking place in Chicago from July 26 to July 31.

Brain Atrophy and Biomarkers May Help Identify People at Risk for Alzheimer’s

Susan de Santi, Ph.D., Associate Professor, Department of Psychiatry, NYU Langone Medical Center

By combining MRI brain scans and measurements of certain compounds in the cerebrospinal fluid, NYU researchers were able to distinguish individuals who would develop Alzheimer’s disease over a two-year period. In a study of 23 people, they found atrophy in areas of the brain involved in learning and memory, and significantly higher CSF levels of phosphorylated tau and other compounds among individuals who would develop Alzheimer’s compared to those individuals who didn’t progress from mild cognitive impairment over the two-year period. This preliminary study suggests that combining these tests could help predict which individuals with mild cognitive impairment are at the highest risk for developing Alzheimer’s disease.
Presentation # P3-067

Big Immune Response to Common Mouth Bacteria Linked to Alzheimer’s.

Angela R Kamer, D.M.D., M.S., PhD., Assistant Professor, College of Dentistry, New York University

In a study investigating the link between Alzheimer’s disease and a heightened inflammatory-immune response, NYU researchers found that twice as many subjects with probable Alzheimer’s disease tested positive for antibodies in their plasma against a type of bacteria that is commonly found in the mouth. The pioneering study supports a growing body of evidence that associates notable immune changes with a means of predicting and classifying Alzheimer’s disease. Together with other immune markers associated with Alzheimer’s disease, antibodies to these periodontal bacteria could serve to better understand the causes and mechanisms of the disease, the researchers say.
Presentation # P1-348

Signs of Brain Disease among Healthy Individuals

Lidia Glodzik, MD, PhD, Research Physician, Center for Brain Health at NYU Langone Medical Center

NYU researchers identified signs of pathology before the clinically noticeable stages of mild cognitive impairment that normally precede Alzheimer’s disease. The study involved a cognitively normal group of people ages 40 to 86. It found that higher levels of tau protein in the cerebrospinal fluid correlated with lower grey matter density in brain regions that are important for learning and memory, and are susceptible to Alzheimer’s. Combining cerebrospinal fluid measurements and imaging markers to identify normal subjects who are more vulnerable to the neurodegenerative disease opens an opportunity to explore early detection in the service of prevention, the researchers report.
Presentation # PS-070

Couples Counseling Helps the Spouse Caregiver

Mary S. Mittelman, Dr.P.H., Research Professor in the Department of Psychiatry at New York University School of Medicine

When the patient with Alzheimer’s and their spouse caregiver are counseled separately, they are expected to go home and live together. Can couples counseling help stabilize their relationship as they grapple with the disease? Early results show that it can. In a pilot study, researchers at NYU’s Silberstein Center offered six counseling sessions focused on the new needs of each member of a couple brought about by the illness. Each of the ill spouses was in the early stages of dementia and could still participate in a counseling session. The NYU researchers report that all caregivers were surprised by how much the person with dementia could communicate in the session. They also report that relationships improved as a result of the counseling, and the caregivers became less depressed.
Presentation # P4-429

Subjective Memory Complaints a Predictor of Further Cognitive Decline

Barry Reisberg, MD, Professor, Department of Psychiatry at NYU Langone Medical Center

An NYU study that followed 213 healthy adults over an average of 7 years found that subjects with subjective memory complaints at the first evaluation were almost 7 times more likely to experience cognitive decline to mild cognitive impairment or dementia compared to adults without initial complaints. This is the first prediction study to link subjective cognitive impairment to both mild cognitive impairment and dementia and underlines the importance in studying early, non-specific symptoms that arise before mild cognitive impairment is apparent, the researchers report. Such efforts are critical to preventing the disease. To develop preventive interventions it may be necessary to accurately identify the disease in its earliest manifestations, when symptoms are first emerging, say the NYU researchers. These subjective symptoms appear to occur as early as twenty or more years before the overt dementia of Alzheimer’s appears.
Presentation # PS-043

A Decreasing Ability to Learn Among Aging Healthy Carriers of APOE 4

Nunzio Pomara, M.D., Professor in the Department of Psychiatry, NYU Langone Medical Center; Director of the Geriatric Psychiatry Program, Nathan S. Kline Institute

A new study by NYU researchers at the Nathan Kline Institute suggests that a major genetic risk factor for Alzheimer’s disease, apoE 4, may exert its adverse effects long before clinical symptoms of the disease emerge. During this critical period they believe there may be a gradually decreasing ability to learn new material, and subsequently form new memories. The scientists evaluated 184 healthy adults, ages 38 to 80 (64 people carried the apoE4 allele), using standardized measures of verbal learning and memory, such as learning a list of words. At younger ages, surprisingly, those with the apoE 4 genetic risk factor significantly outperformed those without it. By ages 60 to 64 and older, however, performance in the apoE 4 group dropped below the non-apoE 4 group.
Presentation # HT-3577

Genetic Mutation Linked to a More Abundant Form of Alzheimer’s Protein

Allal Boutajangout, PhD, Research Assistant Professor, Department of Medicine and Psychiatry at NYU Langone Medical Center

NYU researchers found that a specific gene mutation previously associated with an increase in production of an Alzheimer’s disease-causing protein, amyloid beta, also promotes the entanglement of another protein, tau, which also is associated with the neurodegenerative disease. Mice that produced human types of tau while expressing the gene mutation showed a significant increase in the harmful form of the tau protein in the brain. The research provides a new model for Alzheimer’s onset and progression.
Presentation #04-01-05

Study Further Ties Digestion of Harmful Protein to Alzheimer’s Disease

Dun-Sheng Yang, PhD, Assistant Professor, Department of Psychiatry, NYU Langone Medical Center; Research Scientist, Center for Dementia Research, Nathan S. Kline Institute

NYU researchers genetically enhanced the activity of digestive enzymes in the nerve cells of mice that were susceptible to producing an overabundant amount of amyloid beta, the abnormal protein found in the plaques littering the brains of people with Alzheimer’s. The mice showed lower amounts of the protein in parts of the brain responsible for advanced thinking, learning and memory - evidence that their brain cells were more efficient at digesting and expelling the toxic, misfolded protein, the researchers report. The study shows that the failure to degrade amyloid beta in lysosomes containing the digestive enzymes is an important factor in Alzheimer’s disease. Amyloid beta and another protein called tau are associated with the disease, but it hasn’t yet been proven definitively that either actually causes the disease.
Presentation # P1-059

Study Suggests a Link Between Amyloid and Memory

Paul M. Mathews, PhD, Assistant Professor, Department of Psychiatry, NYU Langone Medical Center; Research Scientist, Center for Dementia Research, Nathan S. Kline Institute

By manipulating levels of the beta amyloid peptide, which accumulates in brain plaques in people with Alzheimer’s disease, NYU researchers have found that the peptide not only plays a toxic role in the neurodegenerative disease but also is crucial in modulating learning and memory consolidation in the normal brain. The rat study, which controlled peptide levels in a region of the brain that is important in learning and memory, suggests that its disruption may be one of the underlying causes of nerve dysfunction during Alzheimer’s disease pathogenesis.
Presentation #02-02-01

Dysfunctional Transporters in Nerves Related to Alzheimer’s

Seonil Kim, Ph.D student, Sackler Institute for Graduate Biomedical Sciences, NYU Langone Medical Center, Graduate Training Program in Cellular and Molecular Biology, Nathan S. Kline Institute and Ralph Nixon, M.D., Ph.D., Professor of Psychiatry and Cell Biology, NYU Langone Medical Center

An NYU study found that membrane vesicles that are essential for the trafficking of materials across nerve cells are an important factor in the pathology of Alzheimer’s disease. Mouse neurons which over-produce a precursor to the amyloid protein closely linked to Alzheimer’s disease development were unable to shuttle the vesicles to their proper destinations in nerve cells, causing them instead to enlarge abnormally and accumulate. The impeded transport of these vesicles, according to the researchers, may affect communications within and between nerve cells that are critical for cognition and when disrupted can lead to the neurodegeneration of Alzheimer’s disease.
Presentation # PS-410

Early Phases of Creating a Vaccine against Prion Disease

Thomas Wisniewski, MD, Department of Pathology at NYU Langone Medical Center

In an animal study, NYU researchers bolstered immunity against a toxic and infectious version of the prion protein, which causes a group of brain diseases, including mad cow’s disease. By injecting a safe, reconfigured form of the protein into the body cavity of mice, in addition to orally delivering a neutral bacterial booster, animals could produce more antibodies against the prion protein in the mouth and blood system, preventing access of the infectious prions to the brain. The inoculated mice remained symptom free for 400 days after exposure to infectious prion, while their brains were free from the disease causing protein. The finding has the potential to safely curb prion diseases, such as chronic wasting disease and variant Creutzfeld-Jacob disease, which are thought to be spread by oral exposure to prion.
Presentation # S3-01-04

Tau Immunotherapy Prevents Cognitive Decline in an Alzheimer’s Mouse Model

Einar M. Sigurdsson, PhD, Assistant Professor of Psychiatry and Pathology, NYU Langone Medical Center

NYU researchers have successfully prevented the cognitive decline of mice by employing a vaccine that targets tangles of tau, a type of protein associated with Alzheimer’s disease. Tests confirmed that the immunotherapy helped preserve cognition as well as reduced tau protein tangles in the brain. The findings support the possibility of an immunotherapy that treats Alzheimer’s disease by directly targeting toxic forms of the tau protein.
Presentation # O4-04-04

Enzyme inhibition modulates Alzheimer’s pathology in mice

Jose Morales-Corraliza, Ph.D, NYU Langone Medical Center and Research Scientist, Nathan S. Kline Institute

CT Researchers at NYU Langone Medical Center and the Nathan Kline Institute found that the inhibition of the calpain enzyme, which is involved in various cellular processes, led to a robust decrease in amyloid deposition in mice that develop plaque pathology commonly seen in Alzheimer’s disease. Modulation of neuronal calpain activity presents a potential therapeutic approach to Alzheimer’s, they report.
Presentation #P1-079

Partial gene-deletion improves memory dysfunction in Alzheimer’s mice

Masuo Ohno, Ph.D., NYU Langone Medical Center and head of the Laboratory of Molecular and Cellular Cognition, Center for Dementia Research at the Nathan Kline Institute

An animal study by NYU researchers reveals that partially inhibiting an enzyme that initiates the release of amyloid beta led to an improvement in neuronal and cognitive deficits in mice that produced excessive amounts of the plaque forming protein. The approach poses a possibility to rescue Alzheimer’s-related deficits, the researchers report.
Presentation #P1-092

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About NYU Langone Medical Center

One of the world’s premier academic medical institutions for more than 167 years, NYU Langone Medical Center continues to be a leader in patient care, physician education and scientific research. NYU Langone Medical Center is internationally renowned for excellence in areas such as cardiovascular disease, pediatrics, skin care, neurosurgery, urology, cancer care, rehabilitation, plastic surgery, minimally invasive surgery, transplant surgery, infertility, women’s health and day surgery.

Source: Bob Brody
NYU Langone Medical Center / New York University School of Medicine

As the world’s attention turns to the global HIV/AIDS epidemic with the convening of the International AIDS Conference in Mexico City, the U.S. Centers for Disease Control and Prevention (CDC) is anticipated to announce on August 3rd significantly higher HIV incidence numbers for the United States. Past estimates have been 40,000 new infections per year; the new number may be more than 25% higher. In reaction to the pending announcement Dr. Gene Copello, Executive Director of The AIDS Institute, issued the following statement:

“Let this serve as yet another wake-up call to our government leaders in Washington, D.C., the States and Territories. We cannot turn our backs on the HIV/AIDS epidemic in our own country. HIV/AIDS is devastating many communities, particularly gay men, African Americans, Latinos and injection drug users. The AIDS Institute calls upon President Bush, the Congress, together with both Presidential candidates, to support a National AIDS Strategy and to demonstrate their leadership by committing immediately to preventing HIV in the United States through increased funding for the CDC HIV Prevention programs, and the establishment and implementation of prevention policies and programs based on sound scientific evidence.

For next year, President Bush has proposed to cut the CDC HIV Prevention budget by $1 million. This is on top of this year’s budget cut of $3.5 million. Neither the U.S. House of Representatives nor the U.S. Senate has proposed any increased funding for HIV Prevention. This is completely unacceptable, particularly in light of the new incidence numbers. Congress must increase funding for HIV Prevention for next year by at least $30 million. This is far from what is needed, but it is, at least, a necessary first step.

The AIDS Institute calls on the Administration, Congress, and the Presidential candidates to support policies and programs that are scientifically known to prevent HIV prevention, such as comprehensive sex education, HIV testing and counseling, and syringe exchange. Further, we call upon our leaders to commit the resources necessary at the National Institutes of Health to conduct behavioral research and to continue to develop such biomedical prevention approaches as microbicides and a vaccine. The government also needs to end programs and policies that are proven not to work, such as abstinence-only-until-marriage programs.

With the revelation that there are more people being infected with HIV in the U.S. each year means more people will be identified as living with HIV/AIDS. It also means they will need adequate healthcare and lifesaving medications to keep them healthy. Again, we must turn to our government to make sure the necessary resources are there for them.

The United States has made a remarkable, and much needed, commitment to global AIDS through the recent reauthorization and expansion of the President’s Emergency Plan for AIDS Relief (PEPFAR). This demonstrated profound leadership on the part of our government. Addressing the HIV/AIDS epidemic at home in our own country requires the same leadership, action, and resolve by our leaders, and those aspiring to become our leaders. The clock is running out, there is no better time than right now to end AIDS in America.”

The AIDS Institute is a national nonprofit agency that promotes action for social change through public policy research, advocacy and education.

The AIDS Institute
http://www.theaidsinstitute.com

WHAT

Several top officials from the World Health Organization (WHO) attending the XVIIth International AIDS Conference in Mexico City will participate in a series of media briefings.

WHO is the directing and coordinating authority on international health and takes the lead within the UN system on the global health-sector response to the AIDS epidemic.

WHO:

- Dr Hiroki Nakatani, Assistant Director-General, HIV/AIDS, Tuberculosis, Malaria, and Neglected Tropical Diseases, WHO
- Dr Carissa Etienne, Assistant Director-General, Health Systems and Services, WHO
- Dr Kevin M. De Cock, Director, HIV/AIDS Department, WHO
- Dr Teguest Guerma, Associate Director, HIV/AIDS Department, WHO
- Dr Paul Nunn, Medical Officer, Stop TB Department, WHO

These WHO officials will be addressing the HIV-related topics listed below, and also will be available for individual interviews.

Monday, August 4

1:00 p.m. Press Conference Room 3, Media Centre, Hall A

WHO media briefing: Reducing deaths from TB/HIV among injecting and other drug users - Meet the experts

It is estimated that one in 10 new HIV infections worldwide are attributable to injecting drug use, and almost one in three new infections outside of Africa. Tuberculosis (TB) is a leading killer of drug users living with HIV. The first-ever policy guidelines to address the risks of HIV and TB co-infection among injecting and other drug users include 13 specific recommendations to expand universal access to HIV and TB prevention, treatment and care services.

Key message: Specially targeted measures needed to reach injecting and other drug users.

- Prof Michel Kazatchkine, Executive Director, The Global Fund to Fight AIDS, Tuberculosis and Malaria
- Dr Kevin De Cock, Director, HIV/AIDS Department, WHO
- Dr Paul Nunn, Coordinator, TB/HIV, Stop TB Department, WHO
- Mr Christian Kroll, Global Coordinator HIV/AIDS, UN Office on Drugs and Crime
- Mr Michael Bartos, Team Leader, Prevention, Care and Support Team, UNAIDS
- Dr Daniel Wolfe, Director, International Harm Reduction Programme, Open Society Institute

Tuesday, August 5

11:00 a.m. Press Conference Room 2, Media Centre, Hall A
WHO press conference: A ‘how-to’ guide for scaling up HIV/AIDS prevention, treatment, care and support interventions in the health sector

WHO will launch a package of priority health-sector interventions designed to help low-and middle-income countries scale up towards universal access to prevention, treatment, care and support by 2010. The publication is designed to be a ‘living’ web-based document that will be periodically updated with new recommendations based on the rapidly evolving experience of health-sector scale up.

Key message: A “one-stop” package describing priority interventions for a health sector response to HIV/AIDS.

Dr Hiroki Nakatani, Assistant Director-General, HIV/AIDS, Tuberculosis, Malaria and Neglected Tropical Diseases, WHO
Dr Teguest Guerma, Associate Director, HIV/AIDS Department, WHO
Hon. Tony Clement, Minister of Health, Canada
Hon. Teodros Adhanom, Minister of Health, Ethiopia
Mr Mark Harrington, Director, Treatment Action Group (TAG)
1:00 p.m. Press Conference Room 1, Media Centre, Hall A
WHO press conference: Interaction of health systems and Global Health Initiatives

- Dr Carissa Etienne, Assistant Director General, Health Systems and Services, WHO
- Dr Kevin M. De Cock, Director, HIV/AIDS Department, WHO
- Dr Julio Frenk, Senior Fellow, Bill and Melinda Gates Foundation
- Dr Jim Yong Kim, Head of Francois Xavier Bagnoud Center for Health and Human Rights, Harvard School of Public Health
- Hon. Emmanuel Otaala, Minister of Primary Health Care, Uganda

Impressive strides have been made with new directed funding streams to HIV/AIDS and other disease-specific programs, such as tuberculosis, malaria, immunization, polio and onchocerciasis. These have included contributions to the building blocks of health systems in many countries such as the establishment and expansion of infrastructure, including labs and clinics. However, there is a growing debate focused on how to increase the benefits as well as guard against adverse consequences of global health initiatives on national health systems. Critics claim that disease-specific initiatives overburden already weak health systems, while others assert that weak health systems are holding back progress in disease specific initiatives. Others say we need to continue disease-specific scale-up efforts and that strengthening health systems requires additional investment. As part of WHO’s effort to gather evidence and provide technical guidance to guide Member States in this area, this media event will reflect the essential features of this discussion.

http://www.who.int

The number of deaths worldwide from AIDS-related causes decreased by 10% in 2007 to two million, compared with 2.2 million in 2007, according to UNAIDS’ 2008 Report on the Global AIDS Epidemic, which was released Tuesday ahead of the XVII International AIDS Conference, the Los Angeles Times reports (Maugh, Los Angeles Times, 7/30).

There were about 2.7 million new HIV cases in 2007, down from three million in 2001 (Executive summary, 7/29). According to the report, about 33 million people in 147 countries are living with HIV/AIDS (Chase, Wall Street Journal, 7/30). Increases in prevention and treatment efforts in the previous two years have contributed to reducing the epidemic’s growth and the death toll (Sternberg, USA Today, 7/30).

The relatively stable number of new HIV cases was fueled by increases in countries such as China, Indonesia, Kenya, Mozambique, Russia and Vietnam, the report found (Los Angeles Times, 7/30). HIV prevalence in some African countries is beginning to level off, but prevalence is increasing in parts of Asia and Eastern Europe, according to the report. About 1.5 million people are living with HIV in Eastern Europe, 90% of whom live in Russia and Ukraine (USA Today, 7/30). About 67% of people living with HIV/AIDS worldwide and 72% of AIDS-related deaths are in sub-Saharan Africa (Cheng, AP/Google.com, 7/29).

The report found that three million people in developing countries are receiving HIV treatment — up from fewer than 500,000 in 2003 — at a cost of $3 billion annually. In Namibia, 88% of people in need of treatment were receiving it in 2007, compared with 1% in 2003. In Cambodia, the percentage of people receiving treatment increased from 14% in 2001 to 67% in 2007 (Los Angeles Times, 7/30). It would cost an estimated $11 billion annually to triple the number of people receiving treatment, the report said (USA Today, 7/30).

The report also found that 33% of HIV-positive pregnant women are receiving treatment to prevent mother-to-child HIV transmission, up from 14% in 2007. The number of new HIV cases recorded among children worldwide decreased to 370,000 in 2007 from 410,000 in 2007, according to the report (Picard, Globe and Mail, 7/30).

The report also found that condom use is increasing among people with multiple sex partners and that adolescents are waiting longer to initiate sex. The percentage of people having sex before age 15 decreased from 35% to 14% in seven African countries, the report said (Los Angeles Times, 7/30).

Governments should continue to invest in HIV treatment and prevention efforts to continue making progress, the report said (AP/Google.com, 7/29). Although a “sixfold increase” in funding for HIV programs in developing countries from 2001 to 2007 “is beginning to bear fruit,” the future of the epidemic is “uncertain” and “intensified action to move towards universal access to HIV prevention, treatment, care and support” is needed, the report said (Dunham, Reuters, 7/29).

Comments, Reaction
UNAIDS Executive Director Peter Piot said the global community has “achieved more in the past five years” toward fighting HIV/AIDS “than in the previous 20 years.” However, if governments “relax now, it would be disastrous,” Piot said, adding, “It would wipe out all of our previous investments” (AP/Google.com, 7/29). “Although we have seen real progress in the last two years, if we want to continue to see results, we will need to see more financial resources and commitment,” Purnima Mane, deputy executive director of the United Nations Population Fund, said (Los Angeles Times, 7/30).

Paul De Lay of UNAIDS added that the global community is “not pushing back the epidemic enough,” noting that there “are still five new infections for every two people who are newly added on treatment.” Paul Zeitz, executive director of the Global AIDS Alliance, added that it is “time to ramp up funding from all sources — not to slow down or go on to other things.” He added, “We’re on the path toward victory here. Let’s invest more” (Reuters, 7/29).

James Chin, a clinical professor of epidemiology at the University of California-Berkeley, said that despite the progress, he is “not sure we will ever get to a point where we can say [HIV/AIDS] is not a public health problem.” He added that until universal access to treatment is “accomplished,” HIV/AIDS will continue to be a public health issue (AP/Google.com, 7/29).

The report is available online.

Kaisernetwork.org is the official webcaster of the XVII International AIDS Conference in Mexico City. Click here to sign up for your Daily Update e-mail during the conference.

Reprinted with kind permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation.

© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

The Drug Information Association (DIA) and the American Association of Pharmaceutical Scientists (AAPS) will co-sponsor Immunogenicity of Therapeutic Proteins (September 10 -12; Bethesda, MD).

Discussion topics will include:

-Current practices in immunogenicity evaluation
-Role of preclinical assessment
-Challenges of clinical immunogenicity assessment: case studies
-Risk assessment and risk management
-Regulatory perspectives
-Future of immunogenicity assessment

“Industry practices in immunogenicity assessment are becoming more unified though challenges still exist in terms of technology and reduction to practice,” says Program Chair Steven J. Swanson, PhD, Executive Director, Medical Sciences, Clinical Immunology Department, Amgen, Inc. “This conference will review key aspects of assay development and validation as well as discuss challenges in implementation of these assays, data interpretation, and relevance to clinical outcomes.”

About the Drug Information Association (DIA)

DIA serves more than 30,000 professionals in the biotechnology, pharmaceutical and regulatory industries worldwide. Through its domestic and international meetings, training courses, workshops and webinars, DIA provides a neutral global forum for the exchange of information critical to the advancement of the drug discovery and lifecycle management processes. Headquartered in Horsham, PA, USA, and with offices in Basel, Switzerland, Tokyo, Japan, and Mumbai, India, the Association is led by its volunteer-based Board of Directors and executive management team.

Drug Information Association

About the American Association of Pharmaceutical Scientists (AAPS)

AAPS is a professional, scientific society of more than 13,500 members employed in industry, academia, government and other research institutes worldwide. Founded in 1986, AAPS provides a dynamic international forum for the exchange of knowledge among scientists to enhance their contributions to public health. AAPS offers timely scientific programs, on-going education, information resources, opportunities for networking, and professional development.

American Association of Pharmaceutical Scientists

Elan Corporation, plc (NYSE: ELN) and Wyeth (NYSE: WYE) are presenting detailed results from the companies’ 18-month Phase 2 study of bapineuzumab (AAB-001) in patients with mild to moderate Alzheimer’s disease at the Alzheimer’s Association’s International Conference on Alzheimer’s Disease 2008 in Chicago, Illinois. As previously announced, in the study, bapineuzumab appeared to have an acceptable safety profile and clinical activity in treating Alzheimer’s disease. Potential efficacy signals were seen at a range of doses without a clear dose response. The study did not attain statistical significance on the pre-specified efficacy endpoints in the overall study population. Post-hoc analyses showed statistically significant and clinically meaningful benefits in important subgroups.

The data will be presented by Sid Gilman, M.D., William J. Herdman Distinguished University Professor of Neurology, Director of Michigan Alzheimer’s Disease Research Center, University of Michigan, and Chair of the independent safety monitoring committee for bapineuzumab.

“This study was limited in its size, design and goals,” said Dr. Gilman, “but if the findings seen in these post-hoc analyses are replicated in the global Phase 3 program, it would be a validation of the amyloid hypothesis and could change how physicians approach the treatment of Alzheimer’s disease.”

Elan and Wyeth believe that the safety and efficacy findings from this Phase 2 trial of bapineuzumab in patients with mild-to-moderate Alzheimer’s disease support the design of the ongoing global Phase 3 program and plan to incorporate learnings from this study into the Phase 3 program. The companies will continue to work diligently to develop much needed new treatment options for patients and physicians.

About the Phase 2 Clinical Trial

The double-blind, placebo-controlled multiple ascending dose trial was designed to assess the safety and tolerability of bapineuzumab in mild-to-moderate Alzheimer’s disease and to explore efficacy at a range of doses. Two-hundred-thirty-four (234) patients were randomized1 to receive one of four doses of bapineuzumab (0.15 mg/kg [n=31], 0.5 mg/kg [n=33], 1.0 mg/kg [n=30] or 2.0 mg/kg [n=30]) or placebo [n=110] by intravenous infusion every 13 weeks. Findings were reported for 229 patients in a modified intent-to-treat (MITT) analysis. Patients were intended to receive up to six doses during the 18-month study.

The pre-specified primary efficacy endpoints were change from baseline in Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and Disability Assessment Scale for Dementia (DAD) in the 0.5 mg/kg, 1.0 mg/kg and 2.0 mg/kg dose groups against their placebo cohorts. Other efficacy measures included change in concentrations of tau in cerebral spinal fluid (CSF), the Neuropsychological Test Battery (NTB), the Clinical Dementia Rating Sum of Boxes (CDR-SOB), the Mini Mental State Examination (MMSE) and brain volume as measured by MRI. Efficacy was assessed from baseline for 78 weeks.

Pre-Specified Efficacy Analysis

In the total study population, statistical significance was not obtained on the pre-specified efficacy endpoints of ADAS-cog and DAD.

Post-Hoc Efficacy Analyses

Modified Intent to Treat (MITT) included patients who received at least one infusion and one efficacy assessment. In analyzing the data, the following were taken into account: an assumption of non linearity of the data over time, ApoE4 carrier status, and baseline MMSE and test scores.

The clinical relevance of the results for patients receiving the full 18 months of therapy was analyzed in a completer analysis. The patients included in the completer analysis received six (6) infusions and a week 78 efficacy assessment.

Using these assumptions, trends in favor of bapineuzumab treated patients were observed in ADAS-cog and NTB in the total MITT population. Additional completer analyses reinforced these trends.

The study revealed important differences in the rate of vasogenic edema by carrier status and for this reason the total population was analyzed by ApoE4 carrier status2.

ApoE4 Non-Carrier Population

In the ApoE4 non-carrier patients, statistically significant differences from baseline to week 78 were observed in favor of bapineuzumab treated patients on both cognitive and functional efficacy endpoints:

-ADAS-cog treatment difference of 5.0; p=0.026
-NTB treatment difference of 0.35; p=0.006
-CDR-SB treatment difference of 1.5; p=0.040

A favorable directional change of 6.9, p>0.10 for DAD was observed.

The completer analysis for non-carrier patients was consistent with the above findings.

Additionally, in these non-carrier patients, MRI results showed significantly less brain volume reduction versus placebo, as measured by the Brain Boundary Shift Integral (BBSI), at 71 weeks3, with a treatment difference of 10.7 cc; p=0.004. Smaller increases in ventricular volume (VBSI) in bapineuzumab treated patients compared to placebo were observed, which were not statistically significant. Progression of Alzheimer’s disease is generally associated with loss in brain volume and increases in ventricular volume.

ApoE4 Carrier Population

In the ApoE4 carrier patients, no statistically significant changes were observed in any of the cognitive or functional efficacy endpoints. The completer analysis for the carrier population showed favorable directional changes on cognitive and functional endpoints. The ongoing Phase 3 studies in ApoE4 carriers will help clarify these findings.

MRI findings in the carrier patients showed no significant change in brain volume between bapineuzumab treated and placebo patients, while a significant increase in ventricular volume in treated patients was observed, mean 2.5cc; p=0.037. The clinical relevance of this finding is still unclear and will continue to be evaluated.

“The clinically significant benefit seen with bapineuzumab treatment in the ApoE4 non-carrier subgroup is encouraging,” said Dale Schenk, Ph.D., Executive Vice President and Chief Scientific Officer of Elan. “These results across multiple endpoints are consistent with what we have seen for beta amyloid immunotherapy from animal studies through to the patients.”

“These data represent scientific validation of our decision to move rapidly into Phase 3 last year,” said Gary L. Stiles, M.D., Chief Medical Officer, Wyeth. “In our Phase 3 program, we will learn much more since we will be able to study bapineuzumab in larger patient populations and better assess the results in ApoE4 carriers and non-carriers in separate trials. We are encouraged by these results and we’ll achieve greater insight as we move forward.”

Safety Findings

Adverse Events (AE) were observed in 95% of bapineuzumab treated patients versus 90% of placebo treated patients. AEs were generally mild to moderate and transient. With the exception of vasogenic edema, AEs did not appear to be dose related.

Adverse events seen in greater than 5% of bapineuzumab treated patients and at twice the rate of placebo treated patients were: back pain; anxiety; vomiting; vasogenic edema; hypertension; weight loss; paranoia; skin laceration; gait disturbance; and muscle spasm.

Three deaths occurred in bapineuzumab-treated patients, though these were not considered by the investigators to be treatment related. No deaths were reported in the placebo group. Other adverse events of interest occurring in less than five percent of patients treated with bapineuzumab included cataract, deep vein thrombosis, syncope, seizures and pulmonary embolism.

Vasogenic Edema (VE)

Twelve (12) cases of vasogenic edema were reported, all in treated patients, and all resolved over time. Ten (10) of these cases were reported in ApoE4 carriers with 2 cases in ApoE4 non-carriers. Eight (8) of the 12 cases were reported in the highest dose group, including both cases seen in ApoE4 non-carriers. Six (6) of the 12 cases were not associated with clinical symptoms and were detected on routine MRI scan. One (1) patient was treated with steroids. Re-dosing was instituted in six (6) of the 12 patients and no recurrence of VE was observed.

Phase 3 Program Implications

The Phase 2 data reinforce the design of the ongoing Phase 3 studies by ApoE4 carrier and non-carrier populations and the selected dose groups. The companies plan to continue all four ongoing Phase 3 studies. The ApoE4 carrier dose in the Phase 3 trials was selected to seek to minimize the risk of VE observed in the Phase 2 trial. The companies intend to obtain feedback from regulatory authorities in the coming months to finalize parameters for the Phase 3 program and discuss and reach agreement on requirements for registration.

About Bapineuzumab

Bapineuzumab is the first humanized monoclonal antibody in late-stage investigation as a potential treatment for Alzheimer’s disease. Bapineuzumab is designed to clear toxic beta amyloid from the brain. The beta amyloid protein is a key component of the neuritic plaques that are implicated in the pathology of Alzheimer’s disease. A global, 4,100 patient Phase 3 clinical program was initiated in December 2007 and is intended to provide safety and efficacy data to support the filing and approval of licensing applications for bapineuzumab as a potential treatment for patients with mild to moderate Alzheimer’s disease. To learn more about this enrollment, patients or caregivers should contact clinical sites directly. Participating clinical sites can be found by visiting http://www.icarastudy.com or, in the United States by calling 1 (888) 818-MEMORY. Study site details also can be found by visiting http://www.clinicaltrials.gov.

About Alzheimer’s Disease

Alzheimer’s disease is a progressive brain disorder that gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate and carry out daily activities, such as bathing and eating. As Alzheimer’s disease progresses, individuals may also experience changes in personality and behavior, such as anxiety, suspiciousness or agitation, as well as delusions or hallucinations. As many as 5 million Americans are estimated to have Alzheimer’s disease, and more than 26 million people worldwide. One in eight baby boomers, and half of all people over 85, will develop the disease.

About the Elan and Wyeth Collaboration

The Wyeth and Elan Alzheimer’s Immunotherapy Program (AIP) includes investigational clinical programs for bapineuzumab. AIP is a collaboration between the two companies to research, develop and commercialize immunotherapeutic approaches that may be used to treat and possibly prevent the onset of Alzheimer’s disease. AIP research focuses on the beta amyloid hypothesis, as the companies believe that enhancing the clearance of beta amyloid in the brain may provide a new treatment approach for Alzheimer’s disease.

About Elan

Elan Corporation, plc is a neuroscience-based biotechnology company committed to making a difference in the lives of patients and their families by dedicating itself to bringing innovations in science to fill significant unmet medical needs that continue to exist around the world. Elan shares trade on the New York, London and Dublin Stock Exchanges. For additional information about the company, please visit http://www.elan.com.

About Wyeth

Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women’s health care, infectious disease, gastrointestinal health, central nervous system, inflammation, transplantation, hemophilia, oncology, vaccines and nutritional products.

Wyeth is one of the world’s largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products, nutritionals and non-prescription medicines that improve the quality of life for people worldwide. The Company’s major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health. For additional information about the company, please visit http://www.wyeth.com.

Safe Harbor/Forward-Looking Statements

The statements in this press release and on the related webcast regarding the companies’ assessment of the Phase 2 data and its implications for the Phase 3 program and future development of bapineuzumab are forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. In particular, these statements are subject to the risk that further analyses of the Phase 2 data may lead to different (including less favorable) interpretations of the data than the analyses conducted to date and/or may identify important implications of the Phase 2 data that are not reflected in these statements. Clinical trial data are subject to differing interpretations, and regulatory agencies, medical and scientific experts and others may not share the companies’ views of the Phase 2 data or its implications for the Phase 3 program and future development of bapineuzumab. In addition, further analyses of the Phase 2 data and discussion with regulatory authorities may lead to important modifications to the Phase 3 program. There can be no assurance that the clinical program for bapineuzumab will be successful in demonstrating safety and/or efficacy, that we will not encounter problems or delays in clinical development, or that bapineuzumab will ever receive regulatory approval or be successfully commercialized. Other risks and uncertainties that could cause actual results to differ materially from those expressed or implied by these forward-looking statements include those detailed from time to time in the Companies’ periodic reports filed with the Securities and Exchange Commission, including Wyeth’s current reports on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K, particularly the discussion under the caption “Item 1A, Risk Factors” in Wyeth’s Annual Report on Form 10-K for the year ended December 31, 2007, which was filed with the Securities and Exchange Commission on February 29, 2008, and Elan’s Reports of Foreign Issuer on Form 6-K and Annual Report on Form 20-F, particularly the discussion under the caption “Item 3D, Risk Factors” in Elan’s Annual Report on Form 20-F for the year ended December 31, 2007, which was filed with the Securities and Exchange Commission on February 28, 2008. The forward-looking statements in this press release are qualified by these risk factors. We assume no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

1 Randomization was on an 8:7 ratio, with more patients receiving bapineuzumab versus placebo.

2 Literature estimates that 40-70 percent of Alzheimer’s disease population are non-carriers of the Apolipoprotein E4 (ApoE4) allele

3 MRI results were measured through week 71

http://www.wyeth.com