Alzheimer's Club

"...Vasogen Inc. (NASDAQ:VSGN; TSX:VAS) is focused on the research and commercial development of technologies targeting the chronic inflammation underlying cardiovascular and neurological disease. The Company's lead product, the Celacade(TM) technology, is currently in two pivotal phase III clinical trials designed to support regulatory approval in North America and commercialization in North America and Europe. The pivotal phase III SIMPADICO trial, which is fully enrolled at 50 centers in North America, is designed to further investigate the use of Celacade technology to improve intermittent claudication, a debilitating symptom associated with peripheral arterial disease. The pivotal phase III ACCLAIM trial, designed to further investigate the use of Celacade technology to reduce the risk of death and hospitalization in patients with advanced chronic heart failure, is fully enrolled at 176 clinical centers in North America, Europe, and Israel. Vasogen is also developing a new class of drugs for the treatment of neuro-inflammatory disorders, such as Alzheimer's disease. VP025, which has completed phase I clinical development, is the lead product candidate from this new class of drugs..."

For further information: Contact: Glenn Neumann, Investor Relations, 2155 Dunwin Drive, Mississauga, ON, Canada, L5L 4M1, tel: (905) 569-9065, fax: (905) 569-9231, www.vasogen.com, investor@vasogen.com

Source: Vasogen to Present at Adams Harkness' 25th Annual Summer Seminar. Canada NewsWire (press release) - Canada (27 July 2005) [FullText]

"Scientists from the Flanders Interuniversity Institute for Biotechnology (VIB) associated with the University of Antwerp have achieved a new breakthrough in their research on the origins of Alzheimer's disease. Their alternative approach opens up new prospects for developing a treatment which can slow the disease's progress. The researchers have shown that 'the plaques' which form in the brain of patients are linked to damage to nearby blood vessels. Leakage appears to occur between the blood vessels and the brain, as a result of which the plaques develop and the disease manifests itself. This research is published in the American Journal of Pathology.

Alzheimer's disease, a degenerative disease that gradually and progressively destroys brain cells, affects between 50% and 70% of all dementia patients and is therefore the major form of dementia. About 100,000 people suffer from this disease in Belgium. The damage caused to memory and mental functioning makes it one of today's most frightening syndromes. In particular, the first realization of the loss of any sense of reality is extremely difficult to accept. So, science continues to search feverishly for ways to treat the disease.

Alzheimer's disease is characterized by an increasing deposit of the amyloid-b protein in the brain. The accumulation of this protein results in 'plaques'; deposits which settle in the brain cells responsible for memory and observation. How the plaques develop is the key in the search for a treatment. Samir Kumar-Singh and his colleagues on a team headed by Christine Van Broeckhoven have unraveled how certain plaques are formed. In various mouse models, they demonstrate that the plaques attach primarily onto the blood vessels. The vessels show clear structural damage, so that the strictly-controlled separation between blood vessels and brain is compromised and leakage occurs.

Under normal circumstances, the blood vessels transport the excess amyloid-beta protein away from the brain. However, the protein has a harmful effect on blood vessel walls. This effect is perhaps strengthened as a result of ageing, which causes the protein to be removed less efficiently. The blood vessel loses strength and in its immediate vicinity the accumulation of the amyloid beta protein increases and plaques develop. Finally, the damage to the blood vessel is so great that it is no longer functional and other blood vessels take over its tasks.

The results of the research of Samir Kumar-Singh opens up alternatives for developing new treatments. For example, a treatment which promotes the removal of the amyloid-b protein from the brain can significantly impede the onset of Alzheimer's disease. A new approach which might have far-reaching consequences. Additional research should make it possible to verify this in greater detail."

http://www.vib.be/

Source: New breakthrough on the origins of Alzheimer's disease. News-Medical.net - World (27 July 2005) [FullText]

"People can battle the effects of the early stages of Alzheimer's disease with memory exercises, research suggests. The exercises, called cognitive rehabilitation, can teach Alzheimer's patients skills and techniques to enhance their memory and functional abilities, said Dr. David Loewenstein, a neuropsychologist with the Wein Center for Alzheimer's Disease at Florida's Mt. Sinai Medical Center.

Researchers developed the program to have relevance with everyday activities. First, patients are asked to identify objects, use them, and recall the items later. Patients also are shown pictures of people to help with face-name association, RTV6's Stacia Matthews reported. "We teach people face-name recognition where they basically learn special techniques to associate names with faces, which is quite problematic for people with memory disorders," Loewenstein said. A study found that after three months of therapy, patients were able to retain the information, Matthews reported..."

Source: Steve Sharp. Program Fights Alzheimer's With Memory Exercises. INDYchannel.com - Indianapolis,IN,USA (27 July 2005) [FullText]

"CHICAGO (26 July 2005) -- Every year, across the United States, thousands of older adults are reported wandering; lost and disoriented. As many as 60 percent of people with Alzheimer's disease or a related dementia will wander, often repeatedly. If not found within 24 hours, up to half of those who wander will suffer serious injury-- even death.

The Alzheimer's Association Safe Return(R) program has a proven 98 percent success rate in returning wanderers. To increase enrollment, the Association has announced efforts to promote greater awareness of the program, made possible through a $250,000 grant from MetLife Foundation.

The grant will fund outreach efforts of three leading association chapters and their regional offices: in Philadelphia, Tampa/St. Petersburg, and Sioux City. These chapters will seek to increase enrollment in the Safe Return program in their communities, as well as plan best practices that can serve as models for Association chapters across the country. These chapters will also work to identify collaborative opportunities to educate and engage audiences to build awareness of the wandering issue and Safe Return.

Originally developed in 1993, Safe Return is an identification, support, and enrollment program working at the community level to provide assistance for a person with Alzheimer's disease or related dementia who wanders off and becomes lost; either locally or far from home. For a one-time enrollment fee of $40, assistance is available 24 hours a day, every day. Since its inception, Safe Return has helped facilitate over 10,000 safe returns. Last year, over 3,000 wandering incidents were reported to the program.

"Wandering is a frightening and potentially life-threatening behavior for those with Alzheimer's," said Sibyl Jacobson, President, MetLife Foundation. "As more individuals are diagnosed with Alzheimer's disease, people need to be made aware of this life-saving and important program."

"We've seen quite positive results with Safe Return, but feel strongly that greater outreach will allow us to make a difference in the lives of many more families," said Kathryn Kane, Senior Vice President of Brand Management and Marketing at the Alzheimer's Association. "We're proud of the success of the Safe Return program, and appreciate the support that MetLife Foundation is providing to help spread the word."

About the Alzheimer's Association: The Alzheimer's Association, the world leader in Alzheimer research and support, is the first and largest voluntary health organization dedicated to finding prevention methods, treatments and an eventual cure for Alzheimer's. For nearly 25 years, the donor-supported, not-for-profit Alzheimer's Association has provided reliable information and care consultation; created supportive services for families; increased funding for dementia research; and influenced public policy changes. The Alzheimer's Association's vision is a world without Alzheimer's and its dual mission is to eliminate Alzheimer's disease through the advancement of research and to enhance care and support for individuals, their families and caregivers. To enroll in Safe Return, or for information on senior safety issues, call 1-888-572-8566 or visit www.alz.org/safereturn.

About MetLife Foundation: MetLife Foundation has supported Alzheimer's disease research and outreach activities for more than 20 years. MetLife Foundation has awarded nearly $10 million in grants through its Awards for Medical Research in Alzheimer's Disease program. It also has a long history of providing support to the Alzheimer's Association in its mission to advance research, public awareness and diversity outreach, as well as enhancing care and support, through initiatives that include caregiving videos, resources for the Hispanic community, and Safe Return. Recently, MetLife Foundation was the sponsor of The Forgetting, an Emmy-winning primetime PBS documentary and outreach program on the disease. For information about MetLife Foundation, please visit www.metlife.org. MetLife is the trade name of Metropolitan Life Insurance Company

Contacts MetLife, Inc. David Hammarstrom, 401-827-2273 dhammarstrom@metlife.com or Alzheimer's Association Pam Rwankole, 312-335-5719"

Source: Business Wire (press release) - San Francisco,CA,USA (26 July 2005) [FullText]

JEFFERSON - The Wisconsin Department of Health and Family Services announced today it is awarding a $59,959 grant to Jefferson County for a project that will promote early identification of Alzheimer's disease and other forms of dementia.

According to Jefferson County Aging/Long Term Support Supervisor Sue Torum, the grant could not have come at a better time. She said the aging population here is growing at a tremendous rate and Alzheimer's disease could one day reach epidemic proportions.

The state's Health and Family Services Secretary Helene Nelson is scheduled to visit Jefferson this afternoon to present the grant to Torum and others at Countryside Home's chapel.

"Early identification of conditions means individuals and families can get the treatment and help they need," Nelson said. "We commend Jefferson County for its vision and work on a Memory Care Connections project to coordinate diagnosis, treatment, information and services to families."

The Jefferson County Human Service Department project is one of four initiatives that will receive grants from the state. Each project is a partnership of medical providers that have formed dementia diagnostic clinics, county offices for aging and long-term support, local providers of dementia care, and the Alzheimer's Association. According to Nelson, the goal is to make it easier for persons with early stage dementia to get a full range of information and assistance.

The state will also award grants to Rock County and to two joint projects - one in Door and Kewaunee counties, and another among Dunn, Chippewa, Barron and Eau Claire counties. These one-year grants are renewable for three years.

The state department earned the federal funds it is providing to Jefferson County in a competitive nationwide process from the U.S. Department of Health and Human Services Administration on Aging.


Memory Care Connections projects are operating in partnership with the Wisconsin Alzheimer's Institute at the University of Wisconsin Medical School. The Institute provides best practice training and current research information to encourage participation in the project by primary care physicians. Memory Care Connections provides nurses and social workers to organize services and caregiver supports.

According to Torum, the grant money that is coming from the state is the total amount requested by the county in its grant application. She said $39,959 will be put toward staffing - which will be the hiring of a project coordinator. The remaining $20,000 will go toward respite services for caregivers.

"This can be extended up to three years at the same rate of annual funding if we fulfill our contractual obligations," Torum said.

Torum said the project coordinator will be hired through the Alzheimer's Association of Southeastern Wisconsin's chapter in coordination with the county. She said the job may be advertised as early as next week in newspapers from Madison to Milwaukee.

Torum said 1,600 people in Jefferson County potentially have dementia at the present time.

"We have more than 12,000 elderly people living in the county and that is more than 10 percent of the 72,000 person population," she said, adding the number of elderly in the county continues to grow as baby boomers approach their senior years.

Torum said that, currently, people with Alzheimer's disease or other dementia are served through several programs. One of these is the Community Options Program. Another is the Medicaid Waiver Program, with an additional one being Alzheimer's Family Caregivers Support Program.

"All those programs provide services and funding to help maintain people with dementia and they are intended to allow these people to continue to stay in their own homes - that is how we do it now," she said, adding that persons interested in being served by those programs should call the county at 674-8139.

With the addition of the grant money this week, Torum said the county's new project coordinator can be hired to be a "highly visible person in Jefferson County and the surrounding communities."

"These services will not be limited to the boundaries of Jefferson County," she said. "We could have restricted it, but we wanted to extend it ... This grant came along at a great time to allow us to get busy on a diagnostic program for early dementia."

Torum said the public will see quite a bit of the project coordinator in the coming year.

"That person will be out in the field at senior centers, senior meal facilities, apartment buildings, and this person will go to any community group that is interested in dementia and Alzheimer's disease," she said. "The coordinator will be able to help lay people spot the symptoms to allow for the delay of the progression of the illness."

The Wisconsin Alzheimer's Institute, a center within the University of Wisconsin Medical School, will be training the project coordinator on using something called the "60-Second Verbal Fluency Memory Screening, which is a tool to help spot dementia.

Torum said the grant goes a long way toward opening up the world of better diagnosis of dementia in the Jefferson County area.

"This grant has given us the opportunity to really pay attention to Alzheimer's and its affects on individuals and their caregivers and really educate the general public on this illness, because it is astounding the impact it has on the community," Torum said. "That is why this grant is so important. With the number of older people growing at such an alarming rate, we have to be prepared to deal with Alzheimer's because it could become an epidemic."

Source: Steve Sharp. News: County gets Alzheimer's grant. Watertown Daily Times - Watertown,WI,USA [FullText]

"ALAMEDA, Calif. (19 July 2005) - Avigen, Inc. (Nasdaq: AVGN - News), today announced encouraging results from the first patient treated in a Phase I/II clinical trial of AV201, the Company's drug candidate for the treatment of mid- to later-stage Parkinson's disease. The results from positron emission tomography (PET) brain scans obtained six months after AV201 infusion indicated an increased activity of the gene product, aromatic L-amino acid decarboxylase (AADC) in the targeted area of the brain, compared with the patient's pre-treatment PET scans. These findings are consistent with increased dopamine production and transgene expression.

In Parkinson's disease, brain dopamine concentrations decline, causing the main symptoms of muscle rigidity, slow movements, difficulty walking, and poor balance. Levodopa, the first-line drug for treating symptoms of the disease requires AADC in order to be converted to dopamine. However, over time AADC production in the brain also declines as Parkinson's disease progresses, making levodopa less effective. The mid- to later-stages of Parkinson's disease are often complicated by the toxic side effects associated with the higher doses of levodopa required to manage the disease's signs and symptoms. AV201 is designed to restore the activity of AADC in the brain, thereby extending the therapeutic usefulness and life of levodopa while avoiding side effects.

The Phase I/II clinical trial of AV201 in Parkinson's disease was initiated in December, 2004, at the University of California San Francisco (UCSF) and Lawrence Berkeley National Laboratory (LBNL). The study's Principal Investigator, Michael Aminoff, M.D., D.Sc., Director of the University of California-San Francisco Parkinson's Disease Clinic & Clinical Research Center, said, "This is an exciting beginning and a first for us: evidence of successful AADC gene transfer into humans. Most importantly for our patient, the procedure and gene appear to be safe. We're pleased with how well AV201 is being tolerated." Dr. Phillip Starr, neurosurgeon for the first patient in the study, added: "Based on the PET scans, it appears that the procedure and the use of convection-enhanced delivery to optimize the spread of AV201 worked as well as we could have hoped. We are enthusiastic about enrolling additional patients."

In another first, by using the dopamine tracer [18F] fluorometatyrosine (FMT)-based PET scanning rather than conventional fluorodopa PET, clinicians were able to visualize evidence of AADC gene expression with greater specificity. The use of FMT-PET technology was pioneered at LBNL by William Jagust, M.D., a neurologist and the Faculty Senior Scientist at LBNL and professor of Public Health and Neuroscience at UC Berkeley, and Jamie Eberling, staff scientist at LBNL and Associate Professor of Neurology at UC Davis. "The tracer is an excellent measure of gene expression," commented Eberling. "FMT-PET studies in animal models of Parkinson's disease have shown sustained AADC gene expression for more than 5 years after convection-enhanced gene delivery, along with sustained motor improvement," commented Dr. Jagust. "In this study, we are evaluating FMT-PET in individuals with Parkinson's disease as a surrogate marker of AADC activity and gene transfer. We are visualizing evidence of successful AADC gene transfer in the human brain for the first time. Both the apparent level and the duration of AADC expression are greater than any of us had anticipated, given the low dose of AV201 with which we began the study."

"These results did exceed our expectations, and we are encouraged that we are on the right track," said Dr. Dawn McGuire, a neurologist and Avigen's Chief Medical Officer. "It is, of course, too early to determine the therapeutic benefit or duration of gene expression. However, the value of this research cannot be underestimated, both for the individuals afflicted with Parkinson's disease and for understanding the potential of gene therapy in neurologic disease."

On April 5, 2005 Avigen announced that it will focus on the development of traditional pharmaceutical products, particularly small molecules and biologics. As part of the decision, the Company indicated it would divest its proprietary AAV technology but was committed to ensuring the continuation of the ongoing clinical programs, including the AV201 Program in Parkinson's disease.

Commenting on the impact of the trial and the strategic decision to reposition the Company, Kenneth G. Chahine, Ph.D., J.D., Avigen's President and CEO, said, "We chose this approach to treating Parkinson's disease not only for its therapeutic potential, but also the potential of visualizing AV201 activity using PET imaging. Therefore, we are very encouraged by these results which underscore the pioneering work of Avigen and its collaborators to provide novel therapeutics for neurological disorders."

Dr. Chahine continued, "This news reinforces the confidence we've always had in our AAV gene therapy program and its potential, but does not change our longer term strategic vision to seek external funding for the AAV technology. At this time, we are in advanced discussions with multiple parties who have the resources and commitment necessary to secure the long-term future and success of our AAV technology, including this very exciting Parkinson's trial. As we move through this process, foremost in our minds is to evaluate our options based on which one will deliver the best long-term value to our shareholders."

About Parkinson's Disease and AV201

Parkinson's disease (PD) is the second most common degenerative neurological disease after Alzheimer's disease, and is characterized by tremor, stiffness of the limbs and trunk, slowness of movement (bradykinesia), and poor balance. PD results from the death of specialized dopamine-producing cells in the brain. More than 2 million individuals in the United States and Europe are afflicted with Parkinson's disease. The primary and most effective treatment for this debilitating movement disorder is oral administration of levodopa, which is converted in the brain by the enzyme AADC, or dopa decarboxylase, into dopamine. As Parkinson's disease progresses, however, levodopa typically becomes less effective, believed due at least in part to the decline in concentrations of AADC resulting from continued neurodegeneration and cell death. Using higher levodopa doses in an attempt to compensate for less efficient conversion to dopamine often leads to intolerable side effects or toxicity. Avigen's AV201 is designed to restore the therapeutic effectiveness of levodopa by infusing the gene for AADC into the brain of patients, thus improving dopamine production. AV201 is an AAV vector containing the gene for human AADC which is delivered directly to the striatum, the part of the brain requiring dopamine to control movement. The patient and physician potentially can regulate the activity of AADC by raising or lowering the amount of levodopa taken. "This functional 'on-off' switch potentially enhances the safety of AV201 gene therapy," commented Dr. McGuire.

Early research conducted in animal models was performed by Krzysztof Bankiewicz, M.D., Ph.D., and Professor of Neurological Surgery at UCSF. Dr. Bankiewicz helped pioneer convection-enhanced delivery, and initiated its use to deliver AAV-AADC in animal models of Parkinson's disease. Studies have demonstrated AADC expression for more than 5 years after a single administration of AAV-AADC, along with continued therapeutic benefit in Parkinsonian nonhuman primates. These results encouraged Avigen to move "from bench to bedside" with the current Phase I-II clinical trial, designed to evaluate the safety of increasing doses of AV201 in individuals with mid-to-later-stage Parkinson's disease.

Participation in This Clinical Trial: Patients or physicians who are interested in learning more about this clinical study, please contact the UCSF Parkinson's Disease Clinic and Research Center Study Coordinator at 415-476-0947.

About Avigen: Avigen, Inc., based in the San Francisco Bay Area, is committed to providing physicians and their patients with innovative therapeutics for the treatment of neurological conditions. Avigen's strength lies in its innovative employees, rigorous science and a focused strategy on treatments for serious and life-threatening neurological disorders. Guided by a strong management team and supported by sound financials, Avigen's strategy is to build a robust pipeline through a combination of internal research, acquisitions and in-licensing with the goal of becoming a fully integrated pharmaceutical company. Additional information about Avigen can be found at http://www.avigen.com .

About Berkeley Lab: Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit the Lab website at http://www.lbl.gov .

Investors Please Note: This news release contains "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding Avigen's expectations for the clinical trial of AV201, the ability of AV201 to restore the activity of AADC in the brain, further successful AADC gene transfers into humans, anticipated enrollment of additional patients in the Phase I/II clinical trial and Avigen's intention to divest its proprietary AAV technology. These statements are not a guarantee of future performance and are subject to risks and uncertainties that could cause actual results to differ materially from those projected in the forward-looking statements. These risks and uncertainties include whether the Phase I/II clinical trial results will validate and support the safety and efficacy of AV201, ability to enroll additional patients, uncertainties related to the timing and completion, if at all, of the divestiture of its proprietary AAV technology, uncertainty in obtaining or maintaining approvals and authorizations required by regulatory or institutional authorities, unanticipated responses to the treatment; and results from the first patient treated with AV201 are not necessarily indicative of results that will be obtained in the clinical trial. In addition, there are many other risks and uncertainties inherent in the development of drug products. Actual results may also differ from those projected in forward-looking statements due to risks and uncertainties associated with the conduct of clinical trials and in Avigen's operations and business. These risks and uncertainties are detailed in reports filed by Avigen with the Securities and Exchange Commission, including Avigen's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. Forward-looking statements contained in this new release are made as of this date and will not be updated."

Source: Avigen Announces Encouraging Early Data From Parkinson's Disease Clinical Trial. Biz.Yahoo.com (19 July 2005) [FullText]

"It's clear that psychological and social factors can affect heart health. The July issue of the Harvard Heart Letter explains that this is a two-way street: The health of your heart and blood vessels also affects your mind and brain.

Among older people, the most common causes of dementia (damage to the brain that leads to memory loss, confusion, and changes in personality or speech) are blood vessel problems and Alzheimer's disease. Research suggests that cholesterol-clogged arteries, inflammation, and risk factors for heart disease and stroke contribute to both, reports the Harvard Heart Letter.

Restricted blood flow in the brain may contribute to the cascade of events that leads to the tangles and clumps of protein in the brain that characterize Alzheimer's. Autopsies show that memory loss and changes in thinking skills and personality are more likely to have occurred when tangles and clumps are accompanied by signs of strokes and narrowed, clogged blood vessels feeding the brain. In other words, improving blood flow to the brain and working to prevent strokes may maintain memory well into old age.

The Harvard Heart Letter recommends these strategies:

1. Exercise. Walk, cycle, garden, dance - better yet, do them all - to keep both brain and body in shape. Research suggests that the variety of exercise, not just how much or how hard you exercise, may help prevent dementia.

2. Keep blood pressure levels low. Untreated high blood pressure speeds aging-related decay in thinking skills and memory.

3. Choose dietary fat wisely. Eating a lot of saturated and trans fat may promote dementia, while omega-3 fats (found in cold-water fish and some plants) may protect against the buildup of protein clumps in the brain."

The Harvard Heart Letter is available from Harvard Health Publications, the publishing division of Harvard Medical School, for $28 per year. Subscribe at www.health.harvard.edu/heart or by calling 1-877-649-9457 (toll free).

Harvard Heart Letter: Harvard Health Publications Harvard Medical School 10 Shattuck St., Ste. 612, Cambridge, MA 02115, United States, http://www.health.harvard.edu

Source: Steps to Prevent Heart Disease May Ward Off Memory Loss. Medical News Today UK (19 July 2005) [FullText]

"NASHVILLE, Tenn. - The Alzheimer's Association is proud to announce the date has been set for Memory Walk Nashville 2005. The walk encourages walkers to participate in fundraising activities to create a world without Alzheimer's disease by joining hundreds from Davidson, Williamson, Sumner, Wilson, and the surrounding areas to raise money for the Alzheimer's Association. The walk will commence at Centennial Park Saturday, October 29, 2005 at 10:00 A.M. (9:00 A.M. registration & pre-walk activities). If you have any questions or are interested in getting involved please contact Caitlin McAleese at (615) 292-4938 x 19.

Proceeds from the Memory Walk directly benefit local programs and services of the Alzheimer's Association. Residents of Davidson and nearby counties are served through Family Care Network support groups, the Safe Return program for wanderers, the Help Line for those in crisis, the Family Relief Fund for low-income caregivers, educational seminars for healthcare professionals, workshops for family caregivers, referrals to healthcare providers and community resources, public policy advocacy for improved legislation, and a community-based resource center.

Members of this year's Memory Walk Planning Committee include: Ron Haskamp, Amy Schmidt, Cindy Natsch, Linda Fowler, Cheryl Jarrell, Janna McGregor, Meredith Webb, Stephanie Morgan-Frye, Terry Zenker, and Chris Snyder.

Memory Walk is the only national fundraiser for the Alzheimer's Association. Although there are over 600 Memory Walks nation-wide, proceeds from the events remain in the local areas.

Alzheimer's is a lengthy, terminal disease that affects the brain. Over 25,000 people in Middle Tennessee have the disease. For every person diagnosed with the disease, the disease significantly impacts at least two caregiver's lives. The mission of the Alzheimer's Association is to serve those with the disease and their caregivers through education, patient and family services, public policy advocacy, and funds to further research."

For more information about Memory Walk or the Alzheimer's Association's services, call (866) 463-6423 or www.alzmidsouth.org.

Contacts: Alzheimer's Association, Nashville Caitlin McAleese, 615-292-4938 ext. 19

Source: Alzheimer's Association Memory Walk 2005 - Nashville. Business Wire (20 July 2005) [FullText]

"New research suggests that accumulation of amyloid-beta peptides in cerebral blood vessels, as opposed to the brain itself, may be a more important pathological mediator of Alzheimer's disease. Two independent yet related articles describe such findings in the August issue of The American Journal of Pathology.
Alzheimer's disease, the most common form of progressive dementia, affects an estimated 4.5 million Americans according to the Alzheimer's Association. Amyloid-beta deposition is a hallmark of Alzheimer's disease and other cerebral amyloid angiopathies. However, exactly how A?ccumulates and causes damage is not fully understood.

In the first article, "Cerebral microvascular Ab deposition induces vascular degeneration and neuroinflammation in transgenic mice expressing human vasculotropic mutant Ab," Miao et al. describe early-onset Ab deposition in Tg-SwDI mice. These mice express Ab protein with mutations that are found in human early-onset cerebral amyloid angiopathy, causing specific accumulation of Ab in cerebral blood vessels.

The Ab peptides accumulated because they could not adequately cross the blood-brain barrier to be cleared from the brain. Over time, Ab accumulation increased in the cerebral microvessels of the thalamus and subiculum of the brain. This resulted in degeneration of blood vessels as evidenced by reduced vessel density and increased apoptosis. Neuroinflammation also occurred as large numbers of microglia, along with inflammatory cytokines, were found at sites of Ab accumulation.

The authors conclude that early-onset Ab accumulation occurs predominantly in the cerebral microvasculature and appears largely responsible for the neuroinflammation in these mice. They also demonstrate the utility of Tg-SwDI mice in studying cerebral amyloid angiopathies, such as Alzheimer's disease.

The second article, by Kumar-Singh et al., "Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls," utilizes two different transgenic mice: Tg2576 and PSAPP. Both models produce dense-core plaques, highly concentrated deposits of Ab and were used to investigate the possible association of blood vessels with A?eposits.

In these mice, dense-core plaques associated with cerebral vessels with high specificity. There was also evidence of vessel damage and blood-brain barrier damage, resulting in release of Ab through the vessel walls and accumulation of plaques next to the vessels. These data confirm previous observations in humans that senile plaques associate with blood vessels, especially in the vasculotropic Flemish type of Alzheimer's disease.

The authors propose a model of dense-core plaque formation that is dependent on cerebral vessels. As Ab is cleared from the brain, it exerts a cytotoxic effect on the endothelial cells of the vascular wall (a process that may be exacerbated if clearance is impaired). This leads to loss of vessel integrity and accumulation of Ab in the area surrounding the compromised vessel wall. Eventually, the damage is so great that the blood vessel deteriorates beyond functional use and new vessels form to pick up the slack. The result is a multicentric dense-core plaque that associates with multiple vessels.

These studies describe several animal models for further examining the pathogenesis and treatment of Alzheimer's disease and related cerebral amyloid angiopathies. And both studies confirm that Ab generated by neurons accumulates in blood vessels following attempted clearance of excess Ab peptides. Thus, study of novel therapies that reduce the blood vessel-associated deposition of A?ay prove beneficial to patients with Alzheimer's disease."

Source: New research suggests that accumulation of amyloid-beta peptides in cerebral blood vessels causes vascular damage in Alzheimer's disease. Medical Research News (21 July 2005) [FullText]

"One puzzle in Alzheimer's disease (AD) research is why mice engineered to have the abnormal protein underlying the disease in humans show little pathology of the disease. Specifically, such mice are genetically altered to overproduce mutant human amyloid precursor protein (APP). It is this protein that, when clipped by enzymes, produces the amyloid beta (Ab) peptide that clusters into the amyloid plaque that clogs the brain and kills brain cells.

The clipping of APP produces two types of amyloid beta peptide--one 40 amino acid units long (Ab40) and one 42 units long (Ab42). Circumstantial evidence has suggested that Ab42 is the "stickier" of the two forms, and underlies the pathology of the disease.

Now, researchers led by Eileen McGowan and Todd Golde of the Mayo Clinic College of Medicine report in the July 21, 2005, issue of Neuron definitive proof that Ab42 is, indeed, the culprit molecule. In their experiments, they created transgenic mice that overproduced either Ab40 or Ab42 in the absence of overproduction of APP. Thus, they could precisely study the role of each of these molecules in AD pathology.

Their studies of the mice revealed that the Ab40 mice showed little amyloid disease pathology in the animals' brains, while the Ab42 mice showed extensive accumulation of amyloid plaque and resulting neural damage. What's more, when the researchers crossed the Ab42 mice with those producing mutant APP, they saw a massive increase in amyloid deposition that was more than the additive effect of the two mutations.

The researchers pointed out that test tube studies have shown that Ab42 aggregates more readily. "Thus, the simplest explanation for the complete lack of pathology in the [Ab40] mice would be the relative inability of Ab40 to initiate nucleation events capable of promoting amyloid deposition," they wrote.

One question the new transgenic mice might help address, wrote the researchers, is whether Ab peptide does damage inside brain cells or outside--"intracellularly." Transgenic mice produced by other researchers have not settled this question, because the peptide was not efficiently secreted by the cells in those mice. However, wrote McGowan and colleagues, "The [Ab] mice that we have developed are clearly distinct from these other "minigene" models in that they efficiently secrete Ab. To date we have little evidence for the accumulation of intracellular Ab in these mice; thus, they provide an excellent tool to study the effects of secreted Ab independently of APP transgenes."

The researchers include Eileen McGowan, Fiona Pickford, Jungsu Kim, Luisa Onstead, Jason Eriksen, Cindy Yu, Lisa Skipper, M. Paul Murphy, Jenny Beard, Pritam Das, Karen Jansen, Michael DeLucia, Wen-Lang Lin, Christopher B. Eckman, Dennis W. Dickson, Mike Hutton, and Todd Golde of the Mayo Clinic College of Medicine, Jacksonville; Georgia Dolios and Rong Wang of Mount Sinai School of Medicine, New York; and John Hardy of the National Institute on Aging, Bethesda. This study was supported by the National Institute on Aging, National Cancer Institute, and by the Mayo Clinic Alzheimer's Disease Research Center. Additional resources from the Mayo Foundation provided by a gift from Robert and Clarice Smith were used to support the Tg2576 mouse colony."

McGowan et al.: "Ab42 is Essential for Parenchymal and Vascular Amyloid Deposition in Mice" Publishing in Neuron, Vol. 47, July 21, 2005, pages 191–199. DOI 10.1016/j.neuron.2005.06.030. www.neuron.org

Contact: Heidi Hardman, Cell Press, hhardman@cell.com or 1-617-397-2879

Source: Pinpointing a culprit molecule in Alzheimer's disease. EurekAlert - Washington,DC,USA (20 July 2005) [FullText]

"The scientists said their success represents a breakthrough that offers hope to the estimated 4 million people who suffer from Alzheimer's disease. The researchers first manipulated the genetic makeup of the mice so they developed dementia; the mice experienced progressive memory loss and also had brain atrophy similar to what a person with Alzheimer's disease experiences.

The mice were then further manipulated so the transgene that causes such symptoms could be "turned off." Transgenes are genes from one organism that have been incorporated into another organism. The researchers predicted that when the transgene expressing the dementia was turned off, memory loss would stop. The results, however, surpassed their expectations, and the symptoms of dementia were reversed - in other words, the mice regained memory.

"Most Alzheimer's disease treatments focus on slowing the symptoms or preventing the disease from progressing, but our research suggests in the future we may be able to reverse the effects of memory loss ..." said Karen Ashe, professor of neurology and lead author of the study. The results appear in the journal Science."

Source: Scientists reverse memory loss in mice. United Press International (15 July 2005) [FullText]

"Research money: $9,164,688 to Dr. Ralph Nixon , $6,692,354 to Dr. Karen Duff

Two researchers at the Nathan Kline Institute in Orangeburg have won separate federal grants for Alzheimer's disease research totaling nearly $16 million.

Dr. Ralph Nixon has been awarded more than $9.1 million from the National Institute on Aging, part of the National Institutes of Health. Dr. Karen Duff was awarded more than $6.6 million from the NIH's National Institute of Neurological Disorders and Stroke.

Both grants will enable the scientists to explore the changes that occur in the brain leading to Alzheimer's disease.

"Alzheimer's is a crucial public-health problem," said Dr. Jerome Levine, interim director of Nathan Kline, a state-run psychiatric research center.

An estimated 4 million people nationwide have the disease, which is marked by progressive loss of memory and cognitive function. That number is expected to rise to 14 million by 2040 as the baby boomers age, according to the national Alzheimer's Association.

Phoebe Colwell of Grand View said she was told by her doctor a year and a half ago that she was showing some early signs of the disease.

The 72-year-old said she takes medications to try to halt the illness. Colwell, who volunteers for the Rockland chapter of the Alzheimer's Association, said research into the disease is valuable.

"You have to try anything and everything," she said.

But she's not hopeful that the results will lead to new treatments to help her. "I don't think we will see a cure in my lifetime," Colwell said.

Researchers said it would take a long time for their work to translate into new treatments for Alzheimer's disease.

Nixon, director of the Center for Dementia Research at the Nathan Kline Institute, said the award will enable him to continue research on tiny parts of the brain cell called endosomes, which show the earliest sign of Alzheimer's disease.

He also is focusing on investigating factors, such as genetics, diet and medication, that might have an impact on the risk of an individual developing Alzheimer's.

Nixon, who also received a $7.7 million grant in 2000 from the National Institutes of Health for research into Alzheimer's disease, said the work is a team effort. Other researchers taking part in the study include Efrat Levy, Paul Mathews, Stephen Ginsberg, Anne Cataldo and Ana Maria Cuervo, he said.

Duff's research focuses on "brain tangles" that result in Alzheimer's disease and other neurodegenerative diseases.

Duff, who this month gave birth on the same day that she found out she was awarded the grant, could not be reached for comment."

Source: Lerner J. Big money for Alzheimer's research. The Journal News.com - Westchester,NY,USA (15 July 2005) [FullText]

"MAYWOOD - Nymox Pharmaceutical Corp.'s application for clearance of its AlzheimAlert urine test kit to help doctors diagnose Alzheimer's disease doesn't provide sufficient proof the product works, U.S. regulators said Thursday. "It is unclear if this device is effective at meeting the stated indications for use," based on existing studies, Food and Drug Administration scientists wrote in a staff review posted on the agency's Web site. The company's shares fell 9.1 percent, their biggest one-day percentage drop in almost a year. The FDA had rejected a previous application for the same doctor-kit form of the test, which now must be processed by Nymox as a laboratory service.

Nymox, which develops drugs and tests for aging-related diseases, will seek to persuade a panel of FDA advisers today in Gaithersburg, Md., to support sales of the kits for doctors to use along with other diagnostic methods.

The urine test measures the presence of a brain protein that is elevated in patients with Alzheimer's, a disease that afflicts as many as 4 million Americans, according to the National Institute on Aging. Shares of Nymox which is based in Maywood and in St. Laurent, Canada, fell 22 cents to close at $2.20 in Nasdaq composite trading, the biggest one-day percentage drop since Aug. 11. The shares have dropped 40 percent in the past 12 months.

AlzheimAlert is certified in the U.S. as a laboratory testing service, and a kit version is available in Europe, Nymox said in a July 8 statement. The test measures the protein as a surrogate marker for the likelihood of the disease. No definitive diagnostic test exists for Alzheimer's, the most common form of dementia, according to the National Institute on Aging.

The telltale plaques and tangles the disease causes in the brain can be conclusively identified only by examining the tissue after death. Clinical diagnoses are limited to "possible" or "probable" cases, according to the institute.

A phone call to Chief Financial Officer Roy Wolvin on Thursday wasn't immediately returned."

Source: Geraldine Ryerson-Cruz. FDA raises questions about Alzheimer's test kit. Bloomberg News (15 July 2005) [FullText]

"WASHINGTON (Reuters) - Tests on mice suggest the brain damage caused by Alzheimer's disease may be at least partly reversible, researchers reported Thursday. Their genetically altered mice regained the ability to navigate mazes after the genes that caused their dementia were de-activated. This suggests that the brain damage caused by Alzheimer's is not permanent, they wrote in their report, published in the journal Science.

"I was astonished. I didn't believe the results when I saw them," said Alzheimer's researcher Karen Ashe of the University of Minnesota, who led the study. "When I saw the memory getting better I actually thought I had done something wrong in the experiment."

Alzheimer's is a brain-destroying disease that affects an estimated 4.5 million people in the United States alone and millions more globally. As the population gets steadily older, experts estimate this number will balloon to as many as 16 million by 2015 in the United States. Outward symptoms start with memory loss, which progresses to complete helplessness as brain cells are destroyed. In the brain, neurons die as messy plaques and tangles of protein form.

The two proteins involved are unhealthy forms of natural brain compounds called amyloid beta and tau protein. Ashe's team worked with mice genetically engineered to develop the mutant tau, but this mutation could be stopped -- or de-activated -- with use of a drug called doxycycline. As expected, the mice developed dementia and had brain atrophy similar to human Alzheimer's disease. And when the engineered gene was turned off, memory loss stopped, as expected. But the mice did not merely stop getting worse. They got better.

"Even mice that had lost half the neurons that are involved in forming memories, when we removed the molecule causing the memory loss from the remaining neurons by turning off the genes, the mice were able to learn and remember new information," Ashe said in a telephone interview. "No one suspected so many neurons would still be able to function."

FROM MICE TO MEN

She noted that it is a long way from treating a mouse to treating a person. "How are we ever going to turn off the gene in humans?" Ashe asked. What might be possible, she said, would be stopping the production of the mutant proteins. And current vaccine efforts are aimed at removing the bad proteins from the brain. "The point that makes us hopeful is the remaining neurons were functioning," she said. "When we removed the molecules that presumably were causing the malfunction, the mice were able to perform better." Ashe said her team used a swimming maze test, in which mice must swim and find an underwater platform to stand on. "The maze situation is very similar to parking a car in the parking lot and remembering where you parked it," she said.

William Thies, vice president for medical affairs at the Alzheimer's Association, said at the very least the mouse would be a useful tool for testing new therapies. "It at least opens the possibility that people will get better," Thies said in a telephone interview. The other interesting finding, Ashe said, was that the tangles of brain cells were not in themselves, evidently, toxic to surrounding brain tissue. "The neurofibrillary tangles, which are one of two major pathological hallmarks of Alzheimers disease, turn out not to be involved in causing memory problems, at least in mice," she said.

Some process may be going on at a microscopic level, and the tangles may be a result but not a cause of the brain damage, she said."

Source: Maggie Fox, Health and Science CorrespondentMouse study suggests Alzheimer's damage reversible AP (14 July 2005) [FullText] [Related reports (total 343 as of 15 July 2005)]

"Advanced warning of the condition could help people make lifestyle changes to reduce their risk

A word recall test can accurately predict whether someone will develop Alzheimer's disease 10 years later, a Canadian study has shown. The use of this test and similar ones could help people concerned about their risk for the condition, says Dr. Mary Tierney, principal investigator of the study and director of the geriatric research unit at Sunnybrook and Women's College Health Sciences Centre in Toronto. "The majority of people don't get Alzheimer's disease -- the majority of seniors are cognitively intact -- so for many it would be reassurance that the probability of getting Alzheimer's disease was low."

People with worrisome scores might have time to examine and adjust lifestyle factors in an attempt to delay the onset of the disease. Increased mental activity, physical activity and social interaction have all been linked to preventing or delaying Alzheimer's disease. The test results would also give people the opportunity to consider future plans, such as advanced directives and living wills, Tierney says.

She and her colleagues studied 263 seniors who took several mental tests in 1991 and were assessed 10 years later. At that time, 47 were diagnosed with Alzheimer's disease. The results of one test, called the short delayed verbal recall test, predicted which seniors would have a diagnosis of Alzheimer's disease 10 years later. The test involves a tester listing 15 common words, which the participant is asked to repeat five times. A second list is then introduced and the participant is asked to repeat those words, and then the words from the original list.

Source: Memory test predicts Alzheimer's disease. Macleans.ca (13 July 2005) [FullText]

"Popular cholesterol-lowering drugs called statins did not protect elderly people from Alzheimer's or other kinds of dementia, a study reports today. Statins are a group of drugs widely prescribed to reduce the risk of heart disease. Recent scientific evidence suggested these drugs also might protect the brain from Alzheimer's. The new findings don't support that hope as yet, but Sam Gandy, an Alzheimer's researcher at Thomas Jefferson University in Philadelphia, says they represent just one piece of evidence in a line of studies that suggested a role for statins in the prevention or treatment of Alzheimer's.

Statins might work as a shield only if given early in life, before the disease has a chance to take hold in the brain, says Gandy, who is also a spokesman for the Chicago-based Alzheimer's Association. The people in the study averaged 75 years old and had been taking statins for an average of five years, says lead researcher Thomas Rea of the University of Washington in Seattle. Their age could explain the negative findings, he says.

Rea and his colleagues studied 2,798 older people who had no sign of cognitive problems at the study's start. The team also kept track of those who developed dementia, including Alzheimer's, over a six-year period. They also noted whether participants were taking statin drugs such as Lipitor or Zocor. Participants took cognitive and memory tests throughout the study. The researchers found that those who took statins developed dementia or Alzheimer's at about the same rate as those who were not taking the drugs. The findings are reported in the Archives of Neurology.

Despite the results, Rea and other experts aren't ready to give up on statins. "We did not find any evidence of protection, but our study is not definitive," Rea says. To get more proof, researchers will have to give a large number of middle-aged people either statins or placebo pills and then check to see whether the people getting the statins are shielded from the disease years later. "Maybe if you start giving these drugs when people are 50 instead of 75, you'll get a better effect," says Larry Sparks, an Alzheimer's researcher at Sun Health Research Institute in Sun City, Ariz.

Sparks has evidence suggesting that statins can help people who already have developed Alzheimer's. His small study published in May shows that atorvastatin (Lipitor) helps boost memory and cognitive ability in people with mild to moderate Alzheimer's. Ongoing studies could help clear up some of the confusion about whether statins can help protect the brain, Gandy says: "We may have some answers later this year.""

Source: Kathleen Fackelmann. Statins fail to hold off Alzheimer's in study. USA Today (11 July 2005) [FullText]

Also see: 34 related reports

"A study of the potential therapeutic effects of the dietary supplement gotu kola is among seven research projects being funded this year by Oregon's Tax Check-Off Program for Alzheimer's Disease Research.

Amala Soumyanath, Ph.D., associate professor of neurology, Oregon Health and Science University School of Medicine, will use the $25,000 grant to continue her work on gotu kola, also known as Centella asiatica. Previous studies, in collaboration with Joseph Quinn, M.D., and Bruce Gold, Ph.D., at OHSU, have shown that gotu kola extracts reverse behavioral deficits in a mouse model for Alzheimer's disease and had protective effects on neuronal cells cultured in the laboratory. The title of her project is "Centella asiatica: a potential therapy for Alzheimer's disease."

"What we plan to do is to conduct in vitro tests using neuronal cells taken from animals, or cultured human neuronal cells to look at ways gotu kola may have beneficial effects in the nervous system in protecting neurons," Soumyanath said. "We're looking at two things: identify the mechanisms by which gotu kola might work; and identify components within gotu kola that have these effects."

She said her ultimate aim is to "be able to carry out clinical trials in human beings. We want to see if gotu kola is of benefit in Alzheimer's patients to relieve or delay cognitive impairment." Herbal products can vary considerably in composition depending on the geographical origin, climatic factors and production method. Information from the current project will help researchers conduct well-designed trials for which the gotu kola preparations have been confirmed to contain the relevant active components.

The Oregon Alzheimer's Disease Research Small Grants Program, funded by the Tax Check-Off Program for Alzheimer's Disease Research, provides grants ranging from $21,100 to $25,000 each for research projects at Portland State University, the University of Oregon, the Portland Veterans Affairs Medical Center and OHSU. The grant period is from June 1, 2005, to May 31, 2006."

Source: Scientist Studying Herb As Alzheimer's Therapy. eMaxHealth (11 July 2005) [FullText]

"Predix Pharmaceuticals, a drug discovery and development company, has initiated the second of two Phase Ib multiple dose studies with PRX-03140, its highly selective, proprietary serotonin 4 (5-HT4) receptor agonist intended to treat Alzheimer's disease and other disorders of memory and cognition. This Phase Ib study is the first Predix study in patients with Alzheimer's disease. The primary objectives of the Phase Ib studies in both healthy subjects and patients with Alzheimer's disease are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the compound over a 14-day period.

This study is a double-blind, placebo-controlled trial, in which patients with mild to moderate Alzheimer's disease receive a once-daily dose of the study drug. The trial will investigate the effects of PRX-03140 on cognitive function and memory, electroencephalograms and biochemical markers of Alzheimer's disease pathology.

"We are pleased to announce that PRX-03140 was well-tolerated in healthy volunteers for 14 days at concentrations that were previously associated with beneficial effects in animal models," said Stephen Donahue, MD, Vice President of Clinical and Regulatory Affairs. "We believe there is a significant unmet medical need for a well-tolerated, effective treatment for Alzheimer's disease that can be given once daily, and we are excited about the early data we are seeing for PRX-03140."

About PRX-03140: PRX-03140 is Predix's second of three clinical drug candidates discovered utilizing computer-generated GPCR models and optimized with integrated computational-medicinal chemistry. PRX-03140 has a selective receptor binding profile, and preclinical studies have shown that it improves cognitive function, as well as increases levels of acetylcholine (ACh), soluble amyloid precursor protein (sAPP) and brain-derived neurotrophic factor (BDNF) in regions of the brain known to be important for memory.

In single and multiple ascending dose studies in healthy volunteers, adverse events have been mild or moderate in intensity, with no serious adverse events or adverse events resulting in discontinuation. The drug concentrations in humans increased in proportion to increases in dose, and results indicate that the drug can be administered once daily. Results suggest that at well-tolerated doses, PRX-03140 is active at the 5-HT4 receptor in humans, and is eliciting central nervous system effects.

About Alzheimer's Disease: An estimated 4.5 million Americans have Alzheimer's disease (AD), with data pointing to a continuing increase in incidence levels. Currently, nearly one in 10 people over age 65 and as many as five in 10 people over age 85 have AD. According to recent research data, by the year 2050, the range of individuals with AD could range from 11.3 million to 16 million.

Acetylcholinesterase (AChE) inhibitors are active provided that endogenous production of ACh is sufficient to maintain local levels. As AD progresses, ACh production declines, and brain levels of this critical neurotransmitter decline. In parallel with effective therapeutics in other neurodegenerative diseases (e.g., Parkinson's Disease), replacement of the prominent neurotransmitter lost in AD should provide significant clinical benefit. However, neither ACh nor its components can be given in sufficient quantities to increase brain ACh levels with tolerable side effects. The search for agents which increase the production and/or secretion of ACh, which can be used alone or in combination with AChE inhibitors, may therefore yield a drug candidate with significant clinical benefit.

About Predix: Predix is a privately held, clinical stage drug development company that uses a proprietary discovery and lead optimization system to develop drugs for G-protein coupled receptor (GPCR) and ion channel targets. Over the past two and a half years, the company has discovered several novel drug candidates, three of which are now in human clinical trials. Predix has initiated a Phase IIa trial with PRX-00023, a 5-HT1A receptor agonist for anxiety and depression, two Phase Ib trials with PRX-03140, and a Phase I trial with PRX-08066, a novel 5-HT2B antagonist for pulmonary hypertension and other hypoxia-associated diseases. For more information on Predix, please visit www.predixpharm.com. Contact: Predix Pharmaceuticals Kim Drapkin, 781-372-3272 or Media Contact: Andrea Johnston, 910-681-1088"

Source: Predix Pharmaceuticals Announces Initiation of Phase Ib Clinical Trial in Alzheimer's Patients; Provides Initial Dose Study Update. Genetic Engineering News (7 July 2005) [FullText]

"Searchers have found the body of a 72-year-old Nova Scotia man with Alzheimer's disease who disappeared Saturday when his wife got out of their car to ask directions.

The body of Placide Trottier was discovered at around noon on Thursday near Antigonish, about 110 kilometres east of Truro. A searcher travelling aboard a Department of Natural Resources helicopter spotted something in the woods, said RCMP Sgt. Frank Skidmore. "We figure he went there the very first day, [it's just that] we couldn't find him.

He said searching for Trottier in the dense woods was "like looking for a needle in a haystack, and unfortunately we found the needle but not to our satisfaction." Trottier drove off on Saturday when his wife got out of their car at a gas station to ask for directions. His Honda Civic was found abandoned on a logging road, with its doors locked, at about 8 a.m. Thursday. Police said Trottier's body may have been lying where it was found for some time."

Source: Elderly man with Alzheimer's disease found dead. CBC News. (30 June 2005) [FullText]

"The Microarray Consortium was initially funded in 2002 by the National Institute of Neurological Disorders and Stroke ( NINDS; http://www.ninds.nih.gov ) and the National Institute of Mental Health ( NIMH; www.nimh.nih.gov ). The new award is supported by these two institutes as well as the thirteen other NIH Neuroscience Blueprint institutes. The consortium combines technology resources from TGen, Duke University in Durham, NC, and the University of California in Los Angeles. Because of the consortium's success and an expanding need for consortium services in neuroscience, a fourth research center, Yale University in New Haven, Connecticut, will be added to the program in June.

About 10,000 investigators from the 15 different NIH institutes that are part of the NIH Neuroscience Blueprint will have access to the technology and expertise within the consortium. These investigators will be able to further their research through the use of microarray technology used for scanning through the entire human genome ( 3 billion letters ) and all of the genes for which it encodes ( 30,000-40,000 genes ).

"The application of the newest and most sophisticated genome scanning technologies will allow us to unlock the mysteries of how the brain functions normally, as well as what causes common human disorders like Alzheimer's disease, multiple sclerosis, and others," said Dr. Dietrich A. Stephan, Director of the Neurogenomics Division at the Translational Genomics Research Institute.

Genomic scanning technologies make use of the human genome sequence to visualize how gene flavors or aberrant amounts of genes can cause human disease. The consortium centers specialize in technologies which provide information about the genes turned on or off in the diseased tissues being studied. Scientists use these microarray technologies to compare genetic patterns between an individual with a disease and an unaffected person. Using this information, investigators can identify the root causes responsible for certain disorders so that diagnostics and treatments can be developed that have a direct impact on the disease mechanisms.

The Microarray Consortium initially received $9 million from the NIH from June 2002 to June 2005, and the new funding will be approximately $25 million over the next five years.

"It is exciting to have the microarray consortium expanded in capacity and expertise to serve the entire community of neuroscientists funded by NIH institutes. The application of genomic technologies in neuroscience is an important step in the development of future therapies for diseases and disorders of the nervous system," said Dr. Thomas Miller, Program Director of Extramural Research Programs at the NINDS.

The consortium worked with 5 AM solutions, a software development company in Phoenix, to create a central database for data generated by the consortium. These data are freely available so the entire scientific community can benefit from this publicly funded endeavor.

The Neuroscience Blueprint institutes are components of the National Institutes of Health in Bethesda, Maryland and are the nation's primary supporters of basic and applied biomedical research on the brain and nervous system. Additional information about the NIH Neuroscience Microarray Consortium can be accessed at http://arrayconsortium.tgen.org.

About TGen

The mission of the Translational Genomics Research Institute ( TGen ) is to make and translate genomic discoveries into advances in human health. Translational genomics research is a relatively new field employing innovative advances arising from the Human Genome Project and applying them to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases. TGen is focused on personalized medicine and plans to accomplish its goals through robust and disease-focused research programs and its state-of-the-art bioinformatics and computational biology facilities.

About Duke

The consortium's site at Duke University will operate in concert with the Institute for Genome Sciences and Policy ( IGSP ). The IGSP, established in 2000 with $200 million in institutional funds, represents Duke University's comprehensive response to the broad challenges of the genomic revolution. IGSP activities are organized through five research centers: the Center for Genome Technology, the Center for Human Genetics, the Center for Human Disease Models, the Center for Bioinformatics and Computational Biology and the Center for Genome Ethics, Law and Policy.

About UCLA

The UCLA Department of Human Genetics provides a world-class research and teaching focal point for campus-wide activities in human genetics and gene therapy. Hailing from the School of Medicine and the College of Letters and Science, the department's diverse faculty is housed in the Gonda Research Center, which offers specialized core laboratories for sequencing and genotyping, array technology, FISH techniques and bioinformatics.

About Yale

The scientific interests of the faculty at Yale represent the full range of the broad and rapidly growing field of neuroscience. Leaders in areas ranging from the genetic and structural analysis of single member channels to the functional characterization of the neocortex are represented among this group of outstanding scientists. The interdisciplinary research programs of Yale neuroscience faculty are central to Yale's Interdepartmental Neuroscience Program ( INP ). This unique, broad-based training program can best be described as a "department without walls," with the primary purpose of providing students with a maximum of diversity and depth in the most important areas of neuroscience research. The neuroscience faculty members at Yale command more than half of the University's biomedical research budget and occupy more than 60,000 square feet of well-equipped laboratory space.

About 5 AM Solutions

5AM provides software solutions and technology services for the biomedical research industry. Life science organizations who view data organization, workflow optimization, analysis and data mining, and geographically independent collaboration as critical to their success are our target customers. Our web-based, interoperable solutions access Laboratory Information Management Systems ( LIMS ), support HIPAA guidelines and enforce 21 CFR 11-compliance, while granting insight into the complex data produced by the "omic" revolution represent the core of our expertise. We share a common passion to advance medicine and science through our contribution of state-of-the-art software development. http://www.5amsolutions.com"

Contact: Galen Perry
gperry@tgen.org
602-343-8423
The Translational Genomics Research Institute
http://www.tgen.org

Source: TGen Press Release ( last viewed 3 July 2005 at I-Newswire ).

"At a recent conference on the prevention of Alzheimer's disease, several new and exciting research findings offered hope for patients and their families. Of course, the obvious finding that I have touted for years is to use your brain or lose it, and there seems to be some support for it. The new label that researchers are using is "cognitive reserve." Scientists have concluded that the brain can continue to grow new neurons throughout life. The more you work your brain to grow the neurons, the greater your cognitive reserve. Just as you have a nest egg for retirement, you'll want to have a reserve of brain function. advertisement

How do you build that reserve? The brain is like a muscle. You have to challenge it by engaging in stimulating activities. Watching television is not enough unless you are tuning into science or other such topics. A sitcom won't do it. As I have advocated in the past, you need to try new mental activities like playing bridge or learning a new language. Taking courses at a college or university can offer a challenge. It is important that you engage in some mental challenge on a daily basis. Clearly, the sooner you start the process of building that reserve the better.

Fortunately, the research has demonstrated that it is never too late to start. So whether you are 50, 60 or 70, now is the time to start or continue building your brain reserve. Another series of studies from the conference suggests that you need to be socially active if you want to reduce your risk of Alzheimer's disease. If you are socially isolated, you have less opportunity for mental stimulation. As we age, we lose family and friends who provided our social environment.

Seek out opportunities to socialize through activities like book groups or even game nights where you participate in mentally stimulating games. You get the mental activity and the socialization. The third line of research from the conference is physical activities. We already knew of links between physical inactivity and chronic conditions like heart disease and diabetes. These affect memory and can lead to dementia. One study found that those who were physically and mentally inactive were more than three times as likely to get Alzheimer's disease as they age. Researchers in Sweden found that those individuals who were obese were more than twice as likely to get Alzheimer's disease. So we need to eat right.

There were a series of studies that discussed diet. Like all research, we need to be cautious about the findings. Consistent with earlier research, heart-healthy diets tend to be good for the brain as well. Another study even suggested that a moderate consumption of red wine or possibly other alcohol could help ward off Alzheimer's disease. On interesting study of identical twins found that daily brushing of the teeth and gums helped lessen the possibility of the disease. Early periodontal disease is a potential precursor of Alzheimer's disease.

If you would like to learn more about the conference and other findings, you can go to www.alz.org for updates. William Arnold is an emeritus professor at Arizona State University and an expert on aging. He welcomes reader comments. You can reach him at william.arnold@asu.edu."

Source: William Arnold. Study: Mental, social stimuli fight Alzheimer's. Arizona Republic (29 June 2005) [FullText]

Excerpt: "In a recent Wall Street Journal opinion piece (registration required), Princeton's Robert P. George teamed up with Dr. Markus Grompe ? "a professor of genetics at the Oregon Health and Science University, director of the Oregon Stem Cell Center and a member of the International Society for Stem Cell Research" ? to herald the promise of an alternative to ethically challenged embryonic-stem-cell research.NRO Editor Kathryn Lopez recently asked George, a member of the President's Council on Bioethics, to talk a little about the future of stem-cell research and some of the heated rhetoric surrounding the issue. National Review Online:Last week in the New York Times, Mario Cuomo wrote "So far neither Mr. Bush nor religious believers have convinced a majority of Americans that the use of embryonic stem cells inevitably entails the murder of a human being. Most Americans, vividly aware of the millions of tragic victims of Alzheimer's, Parkinson's, cancer and spinal cord injuries, believe that embryonic stem cell research may provide cures. They will demand that Congress act to realize that potential..."

...There is another piece of reality that Cuomo is ignoring. He is imagining ? or at least encouraging others to imagine that embryo-destructive research holds the key to curing horrible diseases, such as Alzheimer's, Parkinson's, and cancer. The truth is that we do not know when, or even whether, embryonic stem cells will prove to be useful in treating any disease. Leading authorities on Alzheimer's disease, including many scientists in the field who personally favor embryonic-stem-cell research and its public funding, say that Alzheimer's will almost certainly never be treated (much less cured) by embryonic-stem-cell therapies. A recent story in the Washington Post quoted a leading Alzheimer's researcher as saying that the belief that embryonic stem cells will be used to treat Alzheimer's is a "fairy tale."We cannot say with certainty that embryonic cells will never prove therapeutically useful in treating other diseases, but as a matter of sheer fact not a single embryonic-stem=cell therapy is even in clinical trials. No one knows how to prevent tumor formation and other problems arising from the use of embryonic stem cells. No one knows whether these problems will be solved or solved before other research strategies render embryonic research obsolete. Like John Kerry, John Edwards, and Ron Reagan, Cuomo is elevating the hopes of suffering people and their families who are desperate for cures and eager to believe that if only embryonic-stem-cell research were federally funded they or their loved ones would be restored to health."

A.Koudinov note: Please note that many Alzheimer's top researchers have financial interest in defending other Alzheimer's theories. One example is amyloid theory or amyloid dogma. For the conflict by recent top AD authority, Professor Dennis Selkoe, please see my correspondence with Dr. Selkoe and recent The Wall Street Journal reports . More info on the conflict by Alzheimer's association and other AD researchers see my letter to WSJ .

Source: Scientific BreakthroughsGetting beyond stem-cell ethics obstacles. Q&A by Kathryn Jean Lopez (29 June 2005) [FullText]

"30/06/2005 - A mixture of peptides derived from colostrum could help slow the progression of Alzheimer's disease by reducing the build-up of beta amyloid, a toxic protein that accumulates in the brains of Alzheimer's sufferers, reports Dominique Patton.

ReGen Therapeutics, a UK firm focused on creating drugs for Alzheimer's disease, gained the rights to the polypeptide product Colostrinin in the late 1980s from a Polish research institute.
It initially sought to develop the compound as a pharmaceutical but over the last two years has changed its focus to the nutraceutical market and is now in discussions with partners to market Colostrinin for the 'maintenance of healthy mental function'.

The supplement could be available in North America by next year, according to ReGen chairman and chief executive Percy Lomax.

A double-blind, placebo-controlled trial on 106 people with mild to moderate Alzheimer’s disease, published last year, found that after 15 weeks of taking the product in tablet form, around 40 per cent of the patients were stabilised or had an improved overall response in tests on cognitive function.

The greatest effects were seen in earlier stages of the disease and no serious adverse events were observed during the trial.

The new research, published online in the peer-reviewed journal Neuropeptides on 9 May, reveals a possible mechanism for this effect. Colostrinin appears to prevent the aggregation of beta-amyloid peptide Abeta (1-40) in vitro, dissolving the dense fibres that form in the brain over time.

Dr Marian Kruzel, the company's chief scientific consultant and a co-author of the publication, said: “There is consensus in the scientific community that the production and accumulation of beta amyloid aggregates is central to the pathogenesis of Alzheimer's disease. We believe that this data provides the molecular basis for explaining the beneficial effect of Colostrinin in patients with mild and moderate Alzheimer's disease, which was reported by ReGen last year.”

She added that the study confirms preliminary findings reported at the Alzheimer's Europe conference in Prague last May. They showed that Colostrinin even at very low concentrations can protect nerve cells from the toxic effect of beta amyloid fibrils.

The company is doing further research to clarify the biochemical basis of this action.

Alzheimer's disease is a progressive, neurodegenerative and ultimately fatal disease that slowly destroys the brain. At an advanced stage, Alzheimer's disease sufferers lose the ability to take care of themselves and must be looked after either by family or in residential care homes and hospitals.

A recent conference on Alzheimer's in the US heard that worldwide direct costs of caring for those with the disease and other forms of dementia amount to $156 billion, based on a worldwide prevalence estimate of 27.7 million people with dementia.

With the current trend in demographics, this figure will rise to 34 million by 2025, presenting clear opportunities for supplements targeted at prevention.

Lomax told NutraIngredients.com that the firm was already in advanced discussions with a nutraceutical company active in the US, Canada and Mexico.

"Our most advanced discussions are in the US but we are also talking to marketing partners in Europe, Japan and Oceania," he said, adding that a Colostrinin supplement could be on the North American market next year.

While there will be direct competition in the anti-ageing and cognition market, he believes that "there is nothing directly comparable in the way it works".

The product, thought to contain the fractions of three different proteins, and 81 amino acids extracted from bovine colostrum, is made through a complex manufacturing process, currently being scaled up at Sterling Technology, a leading provider of colostrum products for the US nutraceutical market based in South Dakota.

ReGen says it should have sufficient material available to begin safety studies in the next few months."

Source: nutraingredients.com (30 June 2005) [FullText]

"Dr. Eliezer Masliah, Professor of Neurosciences and Pathology at UCSD, and colleagues at UCSD and Elan Pharmaceuticals in San Francisco, vaccinated mice using a a combination of the protein that abnormally accumulates in the brains of Parkinson's (called human alpha-synuclein) and an adjuvant. This approach resulted in the generation of anti-alpha synuclein antibodies in mice that are specially bred by Masliah's team to simulate Parkinson's disease, resulting in reduced build-up of abnormal alpha-synuclein. The accumulation of abnormal alpha-synuclein is associated with degeneration of nerve cells and interference with normal inter-cellular communication, leading to Parkinson's disease and dementia.

The work marks the first time a vaccine for this family of diseases has been found effective in animal studies. Scientists at Elan Pharmaceuticals have been working for the past few years in a vaccine for Alzheimer's Disease.

The researchers focused on a spectrum of neurological disorders called Lewy body disease, which include Parkinson's and Alzheimer's. These disorders are marked by the presence of Lewy bodies -- abnormal clumps of alpha-synuclein -- in the brain. Normally, alpha-synuclein proteins support communications between brain cells, or neurons. However, when abnormal proteins clump together in the neurons, a build-up of synuclein can cut off neuron activity, blocking normal signaling between brain cells and ultimately choking the cells to death.

"We found that the antibodies produced by the vaccinated mice recognized and reduced only the abnormal form of alpha-synuclein, since the protein's normal form is in a cellular compartment where antibodies can't reach it," said Masliah. "Abnormal alpha-synuclein finds its way to the cell membrane, where antibodies can recognize it."

Masliah stressed that the team's experimental active immunization, while effective in mice, may not be as useful in humans. "We would not want to actively immunize humans in this way by triggering antibody development, because one could create harmful inflammation," he cautioned. "However, it might be feasible to inject antibodies directly, as if the patient were creating his or her own."

The team, the first to identify the presence of these proteins in the human brain, originally thought the protein played an important role in the development of Alzheimer's disease. Then, an explosion of research linked Lewy bodies and their constituent proteins to both Alzheimer's and Parkinson's. The team spent four years clarifying alpha-synuclein's role in Parkinson's, developing a mouse model that contained the faulty and normal genes for alpha-synuclein, and conducting the experiments that led to their current findings.

With evidence that this approach could be effective in treating Lewy Body disease, the UCSD researchers are now working with Elan Pharmaceuticals to develop alternative ways to produce alpha-synuclein antibodies, with the goal of making a vaccine that is safe and effective in humans. While this research could take many years and holds no promise of prevention or cure, the researchers are hopeful that the mouse studies are a step in the right direction.

"This shows the first demonstration of a vaccine for this family of disease," Masliah said.

Co-authors of the paper are Edward Rockenstein, Anthony Adame, Michael Alford, Leslie Crews and Makoto Hashimoto, at UCSD, and Peter Seubert, Michael Lee, Jason Goldstein, Tamie Chilcote, Dora Games, and Dale Schenk, at Elan.

The research was supported by grants from Elan and the National Institute of Aging.

Editor's Note: The original news release can be found here."

Source: ScienceDaily.Com (29 June 2005) [FullText] [UC San Diego Original Press Release]