UT Southwestern researchers have developed a DNA vaccine that helps the body protect against toxic proteins associated with Alzheimer’s disease. These images show amyloid plaque in the mouse brain using plasma containing anti-amyloid antibody from large mammals immunized with the vaccine. Credit: UT Southwestern
A new DNA vaccine when delivered to the skin prompts an immune response that produces antibodies to protect against toxic proteins associated with Alzheimer’s disease – without triggering severe brain swelling that earlier antibody treatments caused in some patients. Two studies from the Peter O’Donnell Jr. Brain Institute demonstrate in animals how a vaccine containing DNA of the toxic beta-amyloid protein elicits a different immune response that may be safe for humans. The vaccine, which will likely be tested further by the FDA, is on a shortlist of promising antibody treatments that may eventually help settle a high-stakes debate of whether amyloid is a vital target for preventing or curing Alzheimer’s.
Dr. Rosenberg notes that earlier research established that antibodies significantly reduce amyloid buildup in the brain, but he needed to find a safe way to introduce these into the body. A vaccine developed elsewhere showed promise in the early 2000s, but when tested in humans it caused brain swelling in some patients. Dr. Rosenberg’s idea was to start with DNA coding for amyloid and inject it into the skin rather than the muscle. The injected skin cells make the amyloid protein, and the body responds by producing new antibodies that inhibit the buildup of amyloid, which some scientists blame for destroying neurons.
Although the DNA vaccine has not yet been tested in humans, it produces a different kind of immune response in the tested animals that significantly lessens the chance of an adverse response in the brain. It shows a DNA vaccine can be effective and safe in 2 large mammals. Most other vaccines only produced an immune response in mice but not large mammals.
More than 5 million Americans have Alzheimer’s, with the number expected to nearly triple by 2050, according to the Centers for Disease Control and Prevention. The vaccine would be more accessible and less expensive and produces a wider variety of antibody types than the preformed antibodies, he said.
A British study from 2008 showed that removing amyloid after it accumulates in the brain does not improve brain cognition. The findings highlight a couple of lingering questions that have crucial implications for the future of Alzheimer’s research: Is amyloid merely a symptom, not the cause of the disease? And if there is causation, can earlier treatments make a difference? Dr. Rosenberg acknowledges that preventing amyloid buildup by itself may not be an adequate treatment for Alzheimer’s, but it could be a major part of the solution. He and other researchers at UT Southwestern are also studying the potential benefits of preventing and removing tangles of toxic tau proteins from the brain.
“Some in the scientific community believe the reason amyloid therapies have failed so far is because too little of the therapy was given, and too late,” Dr. Rosenberg said. “The jury is still out.” Dr. Rosenberg’s latest studies show the potential of a DNA vaccine to prevent the buildup of amyloid in otherwise healthy people. The vaccine was administered to healthy animals, inducing an anti-inflammatory immune response of up to 40X more anti-amyloid antibodies than an earlier vaccine Dr. Rosenberg tested a decade ago.
Dr. Rosenberg expects the FDA will want further tests of the vaccine in its own labs before planning a potential clinical trial on people. If proven effective, the vaccine could be given to people who are at risk of developing Alzheimer’s but have not yet started forming amyloid plaques. http://www.utsouthwestern.edu/newsroom/news-releases/year-2017/may/alzheimers-dna-vaccine.html
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