Could a DNA vaccine help treat Alzheimer’s disease?

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DNA vaccine

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There is a desperate need for a treatment for Alzheimer’s disease. A recent study tested an anti-Alzheimer’s DNA vaccine in mice.

Alzheimer’s disease is an irreversible condition that slowly degrades thinking and memory. It currently affects six million Americans, and that number will increase as the population ages. Many scientists think that it is caused by the build-up of two proteins, called tau and beta-amyloid, in the brain. There is no known cure but many scientists are looking for a treatment. One possible treatment is a DNA vaccine that could stimulate the patient’s immune system to destroy the harmful tau and beta-amyloid proteins.

Researchers in the United States have developed a DNA vaccine that is designed to be injected into the skin. This vaccine contains DNA that encodes part of the beta-amyloid protein. Once injected, the skin cells use the vaccine DNA to produce that bit of the protein. Immune cells in the skin will then make antibodies against this protein. These new antibodies migrate to the brain, where other immune cells will use them to recognize and destroy beta-amyloid as it is being formed.

In their most recent study, the research team injected the DNA vaccine into mice that had been genetically engineered to develop Alzheimer’s disease. They published their results in the scientific journal Alzheimer’s Research & Therapy.

A long-term treatment

For this study, the researchers started injecting the DNA vaccine when the mice were four months old, equivalent to them being young adults. They gave additional injections every one and a half months until the mice were 20 months old. For mice, this is equivalent to late-middle age. The researchers then euthanized the mice and analyzed their brains for signs of Alzheimer’s disease. They compared the brains to brains from the same breed of mice that hadn’t been injected.

No dangerous inflammatory immune response

The researchers monitored the immune response in the mice that received the DNA vaccine. The mice successfully produced antibodies against beta-amyloid, and they didn’t suffer from any inflammatory immune response.

This was an important test because a previous clinical trial in Alzheimer’s disease patients found that directly injecting antibodies against beta-amyloid caused harmful inflammation in the brain.

The DNA vaccine decreased levels of harmful proteins in the brain

In Alzheimer’s disease, beta-amyloid protein forms clumps, or ”plaques”, in the brain. In this study, the DNA vaccine decreased the number of visible beta-amyloid plaques. It also decreased the total amount of beta-amyloid protein in the brains.

Tau protein forms ‘tangles’ in the brains of people with Alzheimer’s disease. Just like beta-amyloid, the DNA vaccine decreased the number of visible tau tangles in the brains of the injected mice. It also decreased the total amount of tau protein.

Still to come: tests in patients with Alzheimer’s disease

The results of this study were very promising. However, there were several limitations. The researchers didn’t actually measure any cognitive symptoms of Alzheimer’s disease in the mice, so it is not clear if the vaccine could actually make a noticeable difference in the life of Alzheimer’s disease patients. This study also started the injections much earlier than would be possible in most actual cases of Alzheimer’s disease.

Despite these limitations, Dr. Roger Rosenberg, the lead researcher for the DNA vaccine project stated, “I believe we’re getting close to testing this therapy in people”. If this therapy is proven safe and effective in humans, it would make a major difference to how Alzheimer’s disease is treated.

Written by Bryan Hughes, PhD

References:

  1. Rosenberg, R. N., Fu, M. & Lambracht-Washington, D. Active full-length DNA Aβ42 immunization in 3xTg-AD mice reduces not only amyloid deposition but also tau pathology. Alzheimer’s Research & Therapy 10, 115 (2018). https://doi.org/10.1186/s13195-018-0441-4
  2. DNA vaccine reduces both toxic proteins linked to Alzheimer’s. The University of Texas Southwestern Medical Center Newsroom. November 20, 2018. https://www.utsouthwestern.edu/newsroom/articles/year-2018/dna-vaccine-alzheimers.html

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