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New Gladstone Institute Aims To Devise Therapies For Alzheimer’s And Other Debilitating Brain Diseases

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A major new research venture that will focus solely on advancing scientific knowledge about brain diseases–such as Alzheimer's disease, HIV-associated dementia, and stroke–was inaugurated today in San Francisco.

The new center is the Gladstone Institute of Neurological Disease, operated by The J. David Gladstone Institutes in partnership with UC San Francisco.
Research will be directed at greater understanding of the biology of neurological disease with the goal of speeding development of new treatment for some of the most prevalent and incapacitating disorders.

Alzheimer's disease affects some four million Americans and is the fourth leading cause of death among adults in the United States. Dementia also afflicts a significant number of AIDS patients, and the National Institute on Aging estimates that Americans suffer nearly 700,000 strokes each year. The new venture brings together six principal investigators and thirteen additional scientists from multiple disciplines who will pool their expertise. The new institute will be located at the UCSF-affiliated San Francisco General Hospital.

"We are in an excellent position to increase our understanding of the processes that result in neurological disease and to hasten the development of therapies for these devastating conditions," said Lennart Mucke, MD, UCSF associate professor of neurology and the institute's director. "I am very excited about the future."

The new institute will build on a 1992 discovery by Gladstone researchers that apolipoprotein E (apoE), a protein involved in cholesterol metabolism, also has profound effects on the growth of nerve cells. Since then, other investigators have found that the inheritance of certain variations of the apoE gene is a significant risk factor for Alzheimer's disease.

"The establishment of this institute reflects the astonishing scientific momentum that has already been achieved under Dr. Mahley's and Dr. Mucke's leadership," said Haile T. Debas, MD, dean of the UCSF School of Medicine and vice chancellor for medical affairs. "UCSF is pleased to have this opportunity to expand an already fruitful collaboration with the Gladstone Institute."

The seed for the new institute was planted in 1996, when Mucke came to UCSF from the Scripps Research Institute in La Jolla, Calif., to direct the newly created Gladstone Molecular Neurobiology Program.

The program, a collaborative effort with the UCSF Department of Neurology, made such rapid progress in studies of Alzheimer's disease and HIV-associated dementia that the decision was made to significantly expand the effort and create an entirely new enterprise, according to Robert W. Mahley, MD, Ph.D., UCSF professor of medicine and pathology and president of the Gladstone Institutes.

Supported by a combination of outside resources and Gladstone funds, the new institute will join the Gladstone Institute of Cardiovascular Disease and the Gladstone Institute of Virology and Immunology, also located at SFGH. "This marks a significant step in the evolution of the Gladstone Institutes," said Mahley.

The Gladstone researchers have worked closely with their neuroscience colleagues on the UCSF Parnassus campus and already have formed a Bay Area Alzheimer's Disease Study Group that brings researchers from leading academic institutions to monthly meetings at UCSF and SFGH.

Under the University's current plans, the new institute will be relocated to UCSF's future Mission Bay campus. This move would allow close collaborations between the Gladstone researchers and other neuroscientists at UCSF. "Our program will contribute to the critical mass of scientists focused on brain research and should form a vital link between basic and clinical neuroscience on the new campus," Mahley said.

The investigators joining forces in the new institute have already made a number of important discoveries:

1. They have found, together with colleagues from other institutions, that so-called "amyloid proteins," which accumulate in brains of Alzheimer's patients in the form of spider web-like deposits, can damage connections between nerve cells that are important for normal brain function.

2. They have observed that molecules involved in brain inflammation after strokes and head injury can increase the accumulation of amyloid proteins in the brain.

3. Most recently, a team of Gladstone neuroscientists have demonstrated that apoE4, a protein that strongly increases the risk of developing Alzheimer's disease in humans, impairs memory and learning in mice. Study results were published September 1 in the Proceedings of the National Academy of Sciences. The animal models used in this research and others developed by Gladstone investigators can be used to test the effectiveness and safety of new treatments before they are used in human patients.

4. In the AIDS field, Gladstone neuroscientists have shown that specific HIV proteins can disrupt the normal function of nerve cells and that, at least in animal models, these effects can be blocked with medications that make nerve cells less excitable.

5. The researchers showed that the human CD4 receptor, the entryway for HIV into immune cells, also may play a role in the degeneration of brain cells in AIDS patients.

The new institute was inaugurated with a one-day scientific symposium today (September 11) featuring distinguished neuroscientists from UCSF and around the country. Among the speakers were Zach Hall, PhD, UCSF vice chancellor for research and former director of the National Institute of Neurological Disorders and Stroke of the NIH, and Nobel Laureate Stanley Prusiner, MD, UCSF professor of neurology, who won the coveted prize in 1997 for his work on prions, particles responsible for some forms of dementia.

"The diseases we study rob people of their memories and of the ability to share thoughts with loved ones. These conditions are so frequent that, sooner or later, almost everybody is touched by one of them, either directly or indirectly through an afflicted relative or friend," Mucke said. "The new Gladstone Institute of Neurological Disease will greatly strengthen UCSF's fight against these illnesses."

The J. David Gladstone Institutes are named for a prominent real estate developer who died in 1971. His will created a testamentary trust that reflects his long-standing personal interest in medical education.

Source: Univ of Ca, San Francisco Press Release: September 11, 1998

Contact: Corinna Kaarlela,, (415) 476-3804

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