New Alzheimer's Vaccine
Reverses Memory Loss
05.31.06
Tampa, FL. (May 31, 2006) - Imagine an Alzheimer's patient receiving a vaccine made of specialized blood cells and then showing a much-improved memory. Also, imagine that vaccine having no side effects and needing to be given only occasionally.
Researchers at the Johnnie B. Byrd, Sr. Alzheimer's Center & Research Institute in Tampa, Florida have not only imagined these things, but they have actually developed such a vaccine that they show reverses memory loss in Alzheimer's mice.
In a study published this week in the journal, Neurobiology of Disease, and currently available on line, researchers took ordinary white blood cells (immune cells) from normal mice. Then they exposed those white blood cells to an abnormal protein called "beta-amyloid." Beta-amyloid accumulates in Alzheimer's brains and appears to be the root cause of this devastating disease. The groundbreaking research was done by investigators from the Byrd Alzheimer's Institute, the University of South Florida, and the University of California.
In the study, a single injection of white blood cells "sensitized" to beta-amyloid was given to Alzheimer's mice who were memory impaired and had Alzheimer's-like brain pathology. When the Alzheimer's mice were tested several months later, their memory performance was surprisingly improved even up to the level of normal mice. Moreover, this single vaccine treatment increased connections between brain cells and reduced brain levels of beta-amyloid in the Alzheimer's mice.
"This adoptive transfer vaccine approach is important not only for the long-term benefits it provides, but also for what it doesn't provide — harmful side effects," Dr. Gary Arendash, Ph.D. emphasized.
Although it is difficult to predict if this adoptive transfer vaccine will be as effective in Alzheimer's patients as the researchers found it to be in Alzheimer's mice, there are a number of reasons why the new vaccine is promising. First, a large number of individuals could be vaccinated at relatively low expense. Second, no drug or adjuvant administration is involved. And third, the vaccine appears safe.
"Theoretically, white blood cells could be withdrawn from an Alzheimer's patient or individuals with the same blood type, the white blood cells could then be sensitized to beta-amyloid, then returned to the patient on a relatively infrequent basis," Dr. Arendash commented.
Plans for clinical trials with the new vaccine in Alzheimer's patients are underway at the Byrd Alzheimer's Center and Research Institute. "Even if this new vaccine does not cure Alzheimer's Disease, it may significantly slow down the disease process and thus provide years of quality life to individuals diagnosed with the disease," said Dr. Arendash.
Exactly how the sensitized white blood cells provide these multiple beneficial effects remains to be determined. "The sensitized white blood cells apparently trigger a long-term and restricted immune response to beta-amyloid in the brain," said Dr. Gary Arendash, a principle investigator in the study. "We suspect that the sensitized white blood cells are activating certain brain cells, astrocytes, to make proteins that are important for brain cell protection and communication between brain cells."
Other vaccine approaches being investigated in Alzheimer's mice and Alzheimer's patients can cause adverse side effects. These include over-activation of the immune system, a trapping of beta-amyloid in the brain's blood vessels, and potentially dangerous brain hemorrhages. Indeed, clinical trials involving direct beta-amyloid injections in Alzheimer's patients were halted due to development of meningoencephalitis in some of the patients and the related death of at least one recipient. By contrast, the new vaccine created by Byrd Institute researchers and their collaborators did not induce an inflammatory response in either the blood or brain of Alzheimer's mice. "We found no evidence of meningoencephalitis, no increase in beta-amyloid in the brain's blood vessels, and no evidence of microhemorrhages in the brains of vaccinated mice," said Dr. Douglas Ethell of the University of California, another principle investigator in the study. "Although Alzheimer's disease is a degenerative brain disease, the immune system plays an important role in the disease process, so vaccines are a viable treatment for the disease," Dr. Ethell indicated.
The researchers cautioned that, although they did not observe undesirable side-effects of the vaccine in Alzheimer's mice, there is no guarantee that side-effects will not be seen in humans. "However, the nature of this new vaccine suggests to us that undesirable side-effects would be very unlikely in Alzheimer's patients," said Dr. Ethell.
"To reverse cognitive impairment through mechanisms that don't involve antibody formation, as we have done, could be a big therapeutic advantage. High blood antibody levels could result in serious complications," said Dr. Arendash. An additional advantage of the new vaccine is that a single injection reverses cognitive impairment for at least 2½ months in mice. Since the researchers did not look beyond that time point, a single vaccine treatment may be effective for well beyond 2½ months. Other vaccine approaches to Alzheimer's disease require weekly or monthly booster injections, with the potential for blood antibody levels against beta-amyloid reaching unsafe levels.
Alzheimer's Disease is a neurodegenerative disease that results in the loss of brain cells and their connections. Signs of the disease usually becomes evident after 65 years of age, initially as a loss of short-term memory for events that occurred a few minutes earlier. Over the disease's time course of 2 to 20 years, cognitive impairment expands to involve long-term memory and language skills. Eventually, all aspects of intellect are lost. Alzheimer's disease currently affects 4.5 million Americans. By the middle of this century, as many as 14 million of today's baby boomers could have AD.
Click here to read the final published version. (PDF)
For more information on the study or on Alzheimer's disease, please visit: www.byrdinstitute.org.
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