Testing the First Alzheimer’s Vaccines

Despite billions of dollars spent on research, the story of developing a drug that can tackle Alzheimer’s is largely one of failure.

This total lack of success has led scientists to focus their attention on another approach – vaccines. They hope that by mobilizing the body to fight the disease they can stop it.

Several very promising vaccine products are already in development, and a landmark trial of one vaccine in Alzheimer’s patients has just begun. Here’s what you need to know…

If a vaccine seems like a strange place to start in the search for a solution to Alzheimer’s, this medical fact might change your mind…

Studies have reported that both the flu and pneumonia vaccines can reduce the risk and incidence of Alzheimer’s by up to 40 percent. This occurs, scientists believe, because these vaccines inadvertently stimulate the immune system to clear toxic, memory-robbing beta amyloid deposits from the brain.

These studies, and other positive findings from earlier research, have encouraged scientists to develop vaccines that target the brain directly.

Alzheimer’s Nasal Vaccine Trial Launched

After two decades amassing preclinical evidence, scientists at Brigham and Women’s Hospital in Boston have launched a clinical trial of a nasal vaccine for Alzheimer’s disease.

Their vaccine works by activating white blood cells in the lymph nodes of the neck. These travel into the brain to clear beta amyloid plaques. Sixteen patients with early Alzheimer’s will test the nasal vaccine to see if it will slow progression of the disease.

Tanuja Chitnis, M.D., professor of neurology at Brigham, explained, saying, “For 20 years, there has been growing evidence that the immune system plays a key role in eliminating beta amyloid.

“Research in this area has paved the way for us to pursue a whole new avenue for potentially treating not only Alzheimer’s, but also other neurodegenerative diseases.”

The University of Texas (UT) has also developed a vaccine. It isn’t delivered nasally but directly into the skin.

Reduces Toxic Proteins by 40 to 50 Percent

In the early development of vaccines, some patients suffered brain swelling. To overcome this, the UT scientists altered the immune response by delivering it into the skin.

After it’s injected this Alzheimer’s vaccine creates a three-molecule chain of beta amyloid causing it to produce antibodies that inhibit the buildup of both amyloid and tau proteins. The latter is important since many scientists now regard tau protein as a bigger threat to the brain than amyloid.

Following successful studies in rabbits and monkeys, the latest study in mice demonstrated a 40 percent reduction in beta amyloid and a 50 percent reduction in tau– all without triggering brain swelling.

Lead scientist Roger Rosenberg said, “This study is the culmination of a decade of research that has repeatedly demonstrated that this vaccine can effectively and safely target in animal models what we think may cause Alzheimer’s disease. I believe we’re getting close to testing this therapy in people.”

In Europe, scientists adopted a different approach to an Alzheimer’s vaccine.

New Amyloid Structure Discovered

To date Alzheimer’s drugs have failed when targeting plaques that have already formed, so these researchers chose to target amyloid in a different way.

The amyloid proteins naturally exist in a highly flexible, soluble form, but in Alzheimer’s they become shortened or “truncated”. The scientists were able to identify an antibody in mice that could neutralize this truncated form and thus prevent the formation of harmful deposits.

They adapted or “humanized” the antibody, called TAP01_04, so the human immune system wouldn’t attack it, and found that it not only attached to the truncated form, but – much to the surprise of the scientists – the amyloid folded back on itself in a hairpin-shaped structure, something that had never been seen before.

This allowed them to engineer a form of amyloid beta that could potentially be used as a vaccine to trigger the immune system to make TAP01_04 type antibodies. When tested in mice, that’s precisely what happened.

“Results Are Truly Spectacular”

Both the “humanized” antibody and the engineered amyloid vaccine, called TAPAS, were tested separately in two different mouse models of Alzheimer’s disease. In both forms researchers saw reduced plaque formation, restored neuron function, increased glucose metabolism in the brain and restored memories.

Professor Mark Carr, a member of the research team, could hardly contain his excitement.

“The results are truly spectacular. I accept that it’s in mice, it’s not in people. But the effects are not marginal. I think you couldn’t possibly ask for more encouraging data.

“We’re very confident that what we see in the mice is very likely to be replicated in humans. The effects that we’ve seen, nothing close to those effects has been seen with anything that people have tried in the last 20 years.

“It dramatically reduces the formation of these plaques, dramatically protects against the loss of nerve cells. I think it is genuinely exciting. Compared to anything that I’ve seen appear in the field, this looks like it will work.”

Let’s hope he’s right.

Testing the First Alzheimer’s Vaccines