10/25/2005

New Study Shows Potential Breakthrough in  ALzheimer’s Treament

Scientists At Blanchette Rockefeller Neurosciences Institute Say Bryostatin May Promote Long-Term Memory

Morgantown, W.Va. -- New research, to be published the week of Oct. 24 in the online Early Edition of the Proceedings of the National Academy of Sciences, suggests that bryostatin may stimulate the production of proteins essential for long-term memory.

"It now appears that bryostatin promotes the synthesis of exactly those proteins necessary and sufficient for brain networks to consolidate memory,” said the study's lead author, Daniel Alkon, M.D., scientific director of the Blanchette Rockefeller Neurosciences Institute. “This could be a real breakthrough for Alzheimer’s patients -- it’s like putting memory proteins in the brain's bank for later use."

Early Alzheimer's patients typically cannot store new long-term memories. Bryostatin biochemically enhances precisely this storage of long-term memory.

Scientists at the Blanchette Rockefeller Neurosciences Institute (BRNI), in collaboration with scientists at the MBL (Marine Biological Laboratory) in Woods Hole, Mass., report in the study that bryostatin can promote the proteins required to construct permanent memory. It has long been known that protein synthesis is needed for storing long-term memories.

The latest research was conducted in the mollusk Hermissenda, a marine snail. By introducing bryostatin to the mollusk in the days leading up to a learning activity, a marked improvement was shown in long-term memory. The improvement is coordinated with a sharp increase in protein synthesis in the subjects.

The scientists used Hermissenda because it has a simple, less complex nervous system, but its ability to learn associations has striking parallels to human learning. “In addition to being able to precisely define the neural networks involved with the learning paradigms, Hermissenda   offers the unique advantages of being able to undergo rapid transition between memory states, and being amenable to drug manipulations affecting memory acquisition and retention simply by immersing the animals in seawater containing the particular drug being tested,” said Alan Kuzirian, MBL associate scientist and co-author of the paper.

Herman Epstein, MBL investigator and study co-author added, “The major insights were gotten in weeks from working with Hermissenda that would have taken months if the work had been done with any other organism.”

Bryostatin was originally developed as a cancer drug, but has been rarely used. It has already been tested in humans for safety, which would allow an expedited path to FDA approval for use in Alzheimer’s treatment. The drug has not yet been subject to human tests for this purpose.

However, scientists at BRNI have demonstrated in earlier studies that bryostatin can improve survival of mice genetically engineered to show the neurodegeneration found in Alzheimer's patients. Bryostatin has also previously been shown to activate enzymes that directly reduce production of the toxic proteins that are abnormally elevated in Alzheimer's disease and lead to the devastating degeneration of brain tissues.

 “This is a significant step in our search for an effective Alzheimer’s drug,” said Robert M. D’Alessandri, M.D., president of the Rockefeller Institute. “We believe we are on the right path toward providing Alzheimer’s patients and their families with a treatment that goes to the underlying cause of the disease.”

The Blanchette Rockefeller Neurosciences Institute, the world's first independent research center devoted to the study of human memory, is associated with West Virginia University and Johns Hopkins University. The Institute was founded in 1999 by U.S. Senator John D. Rockefeller IV, and is named for his mother, who died after a long struggle with Alzheimer's. The Rockefeller family provided $15 million in private support to launch the project. 

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For more information:
Bill Case, HSC News Service, (304) 293-7087
casew@rcbhsc.wvu.edu
lc:10-24-05

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