DNA Vaccine May Protect Against Accumulation of Toxic Amyloid in Alzheimer’s

A new DNA vaccine protects against accumulation of toxic proteins in Alzheimer’s disease, according to new research.

One study, “Evaluation of a DNA Aβ42 Vaccine in Aged NZW Rabbits: Antibody Kinetics and Immune Profile after Intradermal Immunization with Full-Length DNA Aβ42 Trimer,” appeared in the Journal of Alzheimer’s Disease. 

A second study, “Evaluation of a DNA Aβ42 vaccine in adult rhesus monkeys (Macaca mulatta): antibody kinetics and immune profile after intradermal immunization with full-length DNA Aβ42 trimer,” was published in the journal Alzheimer’s Research & Therapy.

Alzheimer’s disease is characterized by progressive deterioration of the brain with significant loss of neurons. One of the hallmarks of the disease is the buildup of amyloid protein, which is key in the pathological alterations in the brain.

Despite the many investigative treatments being tested, including antibodies produced in laboratories, no effective and safe cure for Alzheimer’s exists yet.

Earlier research showed that antibodies significantly reduce amyloid buildup in the brain. However, the induction of brain swelling in some patients indicated that a safer route of administration was needed to efficiently treat the disease.

The research team was led by Roger Rosenberg, MD, a professor of physiology, neurology and neurotherapeutics, and director of the Alzheimer’s Disease Center at UT Southwestern Medical Center.

The scientists injected a new vaccine containing DNA coding for amyloid into the skin rather than the muscle. Upon administration, amyloid is produced and triggers an immune response, which leads to the production of specific antibodies that prevent the accumulation of amyloid.

Importantly, no adverse response in the animals’ brain was observed in the two species tested – monkeys and rabbits. Therefore, although testing in humans will be critical, the DNA vaccine holds potential as an effective and safe approach.

“If you look at the hard reality, the odds are against us because so many therapies have failed through the years. But this has potential,” Rosenberg said in a press release. “We believe this kind of immune response has a high probability of being safe in humans and also being effective to make high levels of antibody.”

According to Rosenberg, the current experimental approach would offer important advantages. “All the vaccines we received as kids and adults have been active vaccinations; we made the antibodies in the body,” Rosenberg said. “It’s safer, more effective, and it’s sustained longer.” The vaccine could also result in a less expensive therapy.

Reducing the amyloid burden in the brain has been a pivotal goal in the fight against Alzheimer’s. Previous evidence has shown that eliminating amyloid after it accumulates in the brain does not improve cognition. Therefore, current research questions whether earlier treatments, potentially targeting other areas of the disease, could make a difference.

“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,” Rosenberg said. “The jury is still out.”

In this regard, the latest studies from Rosenberg’s team showed that the DNA vaccine induced 40 times more anti-amyloid antibodies than an earlier vaccine in healthy animals. This result shows the vaccine’s potential to prevent the buildup of amyloid in people who are at risk of developing Alzheimer’s but have not yet started forming senile plaques.