Vidyya Medical News Service
Volume 6 Issue 67 Published - 14:00 UTC 08:00 EST 7-Mar-2004 Next Update - 14:00 UTC 08:00 EST 8-Mar-2004
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New animal model for Alzheimer vaccine

A study published on Friday, 5 March 2004, describes a promising new primate model for testing a potential Alzheimer's disease vaccine. This may enable scientists to study the vaccine in an animal model of Alzheimer's that is very similar to humans. The goal is to discover the cause of serious side effects that halted an earlier study of the vaccine in people, according to the Alzheimer's Association.

"The animal model described in this study expands the way we might evaluate new vaccine products," said William Thies, Ph.D., Alzheimer's Association vice president for medical and scientific affairs. "Vaccination against amyloid is a reasonable strategy for preventing and possibly treating Alzheimer's and this study brings us one step closer. Having more model systems that are closer to humans increases the likelihood that we can avoid the kind of side effects that we saw in the first human trial."

"Tremendous progress has been made by the National Institute on Aging, the Alzheimer's Disease Centers, universities, pharmaceutical companies and the Alzheimer's Association in understanding Alzheimer's disease. The Association's goal of delaying the disabling symptoms and eventually preventing Alzheimer's appears to be a feasible objective that the research community can achieve in the next decade," Thies added.

"Alzheimer Aß Vaccination of Rhesus Monkeys (Macaca Mulatta)," by Sam Gandy, M.D., Ph.D., and colleagues, appears in the March 2004 issue of the journal Alzheimer's Disease and Associated Disorders.

"This may prove to be a helpful model system for us to discover why some humans develop brain inflammation when they are vaccinated with beta amyloid," said Gandy, of the Farber Institute for Neurosciences at Thomas Jefferson University, Philadelphia. Gandy is vice chair of the Alzheimer's Association's Medical & Scientific Advisory Council.

According to Gandy, because of Rhesus monkey's genetic similarity to humans, this study was initiated to determine whether the brain changes associated with vaccination of humans could be modeled in aged nonhuman primates. Gandy believes he and his team were successful.

"These monkeys respond to the vaccination by producing lots of antibodies to Alzheimer amyloid and by showing elevated plasma amyloid that is presumably on the way being cleared from the body. We also examined the brains after six months of vaccination. There was no evidence of inflammation," Gandy said.

Alzheimer Vaccination
Mouse models of Alzheimer amyloid vaccination have shown excellent results. Vaccination of plaque-forming transgenic mice with aggregated Alzheimer amyloid beta peptide has shown that it can promote clearance of existing deposits of Alzheimer-type cerebral amyloid and reverse amyloid associated behavioral deficits in mice.

A trial in humans was stopped in 2002 because a small percentage of participants developed symptoms of inflammation of the brain and spinal cord. However, we still have much to learn from that trial, according to the Association.

A preliminary report published on a small subgroup of the vaccine trial population indicated positive results in stopping or significantly reducing cognitive decline in those participants who developed antibodies to beta amyloid. And, in the first autopsy report of a participant in the vaccine trial, scientists found evidence that significant areas of her brain were free from the amyloid plaques targeted by the vaccine - a phenomenon not seen in the brains of seven unvaccinated individuals with Alzheimer's who participated in the study.

"This possible plaque reduction represents the first time that a medication has shown evidence of modifying a fundamental feature of Alzheimer pathology in a human being," Thies said.

In a review article published in the same issue of the journal, Gandy and colleagues said, "These recent data clearly demonstrate that tackling beta amyloid plaques by vaccination is a feasible approach for preventing or even treating A[lzheimer's] D[isease]-associated pathology. However, more fine-tuning in guiding the immune response is needed to circumvent detrimental side effects."

About The Study
In this proof-of-concept study, Gandy and colleagues vaccinated two rhesus monkeys with beta amyloid, a protein fragment considered a prime suspect in disrupting and destroying nerve cells in the Alzheimer brain. The vaccinated monkeys developed significant levels of antibodies to beta amyloid as well as high levels of beta amyloid circulating in their blood, much of it attached to antibodies.

Two other monkeys were vaccinated with a "control" amyloid: in this case, the islet amyloid that builds up in diabetes. They did not develop antibodies against beta-amyloid and had much lower circulating beta-amyloid levels. None of the four monkeys showed any evidence of brain inflammation.

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