METLIFE FOUNDATION ANNOUNCES MAJOR AWARDS TO SCIENTISTS

METLIFE FOUNDATION ANNOUNCES MAJOR AWARDS TO SCIENTISTS

February 29, 2008

The winners of the annual MetLife Foundation Awards for Medical Research in Alzheimer’s Disease were announced in Washington, D.C. today. Awards were made at a special scientific briefing and luncheon to three scientists who have all individually made significant contributions to the understanding of Alzheimer's by shedding light on beta-secretase and gamma-secretase enzyme activities in the brain - enzymes that play an important role in Alzheimer's disease. Bart De Strooper, M.D., Ph.D.  of Belgium’s K.U.Leuven and VIB-Institute for his work on the cell biology of the amyloid precursor protein and gamma-secretase; Robert J. Vassar, Ph.D. of Northwestern University for his research on the beta-secretase enzyme and molecular mechanisms of Alzheimer's disease; and Philip C. Wong, Ph.D. of the Johns Hopkins University School of Medicine for his work on molecular mechanisms and experimental therapies for Alzheimer's disease.

Since 1986, MetLife Foundation has granted major awards to scientists who have demonstrated significant contributions to the understanding of Alzheimer's disease. At the heart of the awards program is a strong belief in the importance of basic research, with an emphasis on providing scientists with the opportunity to pursue their ideas. Each of the winners will receive a $25,000 personal award, in addition to a $175,000 award to each of their institutions, to further their research.

“The aging of the population means, unfortunately, that the impact of Alzheimer’s will increase in the coming years,” said C. Robert Henrikson, Chairman, President and Chief Executive Officer of MetLife, Inc. “The impact of Alzheimer’s on families, society, and the economy is why MetLife Foundation has been committed for over 20 years to the search for a cure.”

Worldwide, some 24 million people have dementia, with Alzheimer’s disease being the most common cause of dementia. The social, emotional, and economic consequences of Alzheimer’s are staggering, and are expected to grow in the years to come, particularly in countries with large Baby Boomer populations, such as the United States. There are more than 5 million people with Alzheimer’s in the United States alone. Direct and indirect annual costs of caring for individuals with Alzheimer’s disease and other dementias, including Medicare and Medicaid costs and the indirect cost to business of employees who are caregivers of persons with Alzheimer’s, amount to more than $148 billion annually, according to estimates used by the Alzheimer’s Association.

“These awards are an investment in the future. Scientists represent our best hope for one day finding the causes and treatments for Alzheimer’s,” said Sibyl Jacobson, president, MetLife Foundation. “We thank the awardees for their important contributions to the understanding of Alzheimer’s and commend their continued dedication to scientific research.”

The event’s keynote speech was delivered by noted actor, author, and Alzheimer's advocate Kate Mulgrew. The popular actress, who has appeared on television, stage and screen, mostly notably as Captain Kathryn Janeway in Star Trek- Voyager, has had a long-standing commitment to Alzheimer’s and is a member of the Alzheimer’s Association National Advisory Board. She was recently featured in the National Alzheimer’s Association awareness campaign. Her recollections of her mother, who was diagnosed with Alzheimer’s, are found in the recently published book, Voices of Alzheimer’s.

The awards program began with a research briefing, where the award recipients discussed their work. The briefing was moderated by Robert N. Butler, M.D., president and chief executive officer of the International Longevity Center - USA, and Professor of Geriatrics, Mount Sinai Medical Center in New York City. Dr. Butler is the chair of the MetLife Foundation’s Research Committee and also the founding director of the National Institute on Aging of the National Institutes of Health.

“As the population ages, research on Alzheimer’s disease has never been more important,” said Dr. Butler. “If unchecked, the medical and caregiving costs could very well make Alzheimer’s the most significant disease of this century. However, it’s the personal costs that are truly staggering, because Alzheimer’s gradually robs individuals of the person that they once knew. Through this annual award, MetLife Foundation has demonstrated sustained support for scientists working to unravel the mystery of Alzheimer’s, by providing leading scientists with the funds to freely pursue their ideas and attest to the progress and promise of research.”

About the Award for Medical Research Winners

Dr. De Strooper is head of the VIB Department of Molecular and Developmental Genetics, K.U.Leuven (Belgium) where he operates the Laboratory of Neuronal Cell Biology. A recipient of the Potamkin Prize, the Alois Alzheimer's Award and the Pioneer Award from the Alzheimer's Association, Dr. De Strooper's multinational research group has shown the central role of presenilin in the production of amyloid beta in brain cells and the essential role of presenilin in the cleavage of the Notch protein, a major regulator of brain and immune function.

The two findings set the stage for worldwide efforts to identify gamma-secretase blockers to treat Alzheimer’s without side effects caused by blocking Notch signaling, and began a decade long inquiry involving researchers from more than 15 countries that has led to dramatic improvements in scientists' understanding of the gamma-secretase protein complex. Most recently it has been shown that the gamma complex is actually four similar sub-complexes, that one of the sub-complexes is more active in the brain and that this sub-complex activity can be blocked without major side effects in mouse models. Dr. De Strooper’s team is currently developing new therapies targeted at inhibiting gamma-secretase activity and screening drugs designed to do the job.

Dr. Vassar is an associate professor in the Department of Cell & Molecular Biology at the Feinberg School of Medicine at Northwestern University in Chicago.  Dr. Vassar's latest work includes innovative explorations that could lead to gene therapy for the treatment of Alzheimer’s. He and his colleagues are looking at whether RNA-interference of the beta-secretase enzyme known as BACE1 can be used to reduce plaque levels in mouse models of Alzheimer’s. They have already shown that genetic deletion of BACE1 prevents amyloid beta-dependent memory deficits, brain cell loss, and plaques in mice. He is also working on the regulation of BACE1 in the brain and the role the enzyme plays in the development of Alzheimer’s disease.

Previously, while leading a research team at Amgen, Dr. Vassar and his colleagues were the first to clone and characterize BACE1 and subsequently set out to validate that it was responsible for wreaking havoc in the brain. By creating mouse models without the gene for BACE1, Dr. Vassar demonstrated that the brains of such mice were free of the amyloid beta peptide and that the mice appeared otherwise normal with no obvious side effects from the absence of BACE1.  The studies reinforced that BACE1 inhibition is a very promising target for Alzheimer's treatment. The team's 1999 publication of their findings in Science magazine intensified scientists' investigations into beta-secretase and launched the quest for small molecule inhibitor drugs.

Dr. Wong is an associate professor in the Departments of Pathology and Neuroscience at the Johns Hopkins University School of Medicine. In 1997, Dr. Wong was among the first to publish findings indicating the central role of presenilin in the development and regulation of the communication pathway between brain cells, known as the Notch signaling pathway. Dr. Wong's discovery that knocking out presenilin activity disrupts proper development of this pathway pointed to the need for therapies highly targeted to the specific secretase enzymes involved in amyloid beta production.

Influenced by Dr. Robert Vassar's work, Dr. Wong’s team moved quickly to develop mouse models with the BACE1 gene knocked out, and validated that the enzyme is an attractive therapeutic target for Alzheimer’s. Examining the neurons of his mice, Dr. Wong demonstrated that while beta-secretase elimination could have adverse effects on a developing brain, these effects may not show up in a mature brain. Dr. Wong turned his attention to the second cleaver in the amyloid beta production process, gamma-secretase. Ongoing research on gamma-secretase has led to the discovery that it is not a single protein enzyme but rather a series of enzyme complexes comprised of four different proteins.  By developing mouse models with each of the gamma secretase genes knocked out, Dr. Wong’s team showed that moderate inhibition of gamma secretase provides benefits in the brain without adverse side effects.  His latest work includes the development of methods to deliver therapeutic drugs designed to inhibit beta- and gamma-secretases directly into the brain to avoid the side effects of treatment outside the brain.