Will dementia vaccines ever become reality?

Vaccines are arguably one of the greatest inventions of medical science of all time. This strategy is now being applied to the treatment and prevention of Alzheimer’s. As the amount of older Canadians increases over the next few decades, the number of Alzheimer’s cases is expected to skyrocket. Researchers are looking to take vaccine technology one step further to protect against neurodegenerative diseases like dementia.

Dementia is an umbrella term that refers to a range of disorders that affect the way in which a person’s brain works, causing symptoms including memory loss, behaviour changes, and difficulty speaking and walking. The most common form of dementia is Alzheimer’s disease, which accounts for 60% to 80% of dementia cases. More than 55 million people around the world have dementia, with about 10 million cases added each year.

There are some Food and Drug Administration (FDA)-approved drugs for Alzheimer’s disease aimed at either changing disease progression or helping lower some symptoms of the condition. However, as of now, there is no cure for the condition or treatment option to reverse the cognitive impairments caused by Alzheimer’s disease. Traditional vaccines, such as vaccines for the flu and shingles, train the body’s immune system. Vaccines against neurodegenerative disorders are like subunit vaccines — using only a piece of the pathogen — and recombinant vaccines using DNA technology to raise antibodies against the most immunogenic peptide segments.

It is a dynamic time in Alzheimer’s disease research, as there are currently at least nine vaccines in clinical trials for Alzheimer’s and cognitive impairment — six of which are in Phase 2 or 2b trials, on the way to Phase 3. There is also some research exploring active immunization, such as vaccines, to ‘protect’ individuals from Alzheimer’s. The aim is that with better biomarkers and diagnostics, people at risk of Alzheimer’s can be identified in an asymptomatic state five to 10 years earlier. At that stage, administering a vaccine, perhaps combined with other treatments, could prevent the onset of the disease or reduce its severity.

In Alzheimer’s disease, the following processes develop in the brain tissues:

Beta-amyloid plaques are formed from beta-amyloid protein. Inside the neurons of the brain, neurofibrillary tangles are formed from hyperphosphorylated tau protein. These accumulations of beta-amyloid and tau protein lead to the destruction of neurons and the development of inflammatory processes. As a result, neurons and the connections between them vanish, and memories, the ability to create them, and other human cognitive functions — thinking, the ability to concentrate on a task, logic, gradually wane off. The aggregation of beta-amyloid is the critical feature for initiating Alzheimer’s disease followed by accumulation of pathological tau and downstream inflammation, oxidative stress, and neurodegeneration. On average, people with Alzheimer's disease live between three and eleven years after diagnosis, but some survive 20 years or more.

Dementia vaccines under development

A number of dementia vaccines are currently in different stages of clinical trials to study their effectiveness and safety, including:

• a nasal Alzheimer’s disease vaccine from Brigham and Women’s Hospital in Boston entered the phase 1 clinical trial stage in November 2021

• a phase 2 clinical trial is underway for Araclon Biotech’s Alzheimer’s disease vaccine targeting beta-amyloid 40

• Swiss-based biopharmaceutical company AC Immune SA has a tau-targeted vaccine candidate for Alzheimer’s disease in a phase 1B/ 2A clinical trial.

Will dementia vaccines really work?

While these findings do offer hope, it’s far too soon to know if and how the vaccine will work on humans. According to health experts, it will be years, maybe even decades, before we have a vaccine ready for humans. And that’s if the vaccine actually works. If the tau protein is, in fact, the cause of Alzheimer’s disease, scientists will also need to figure out how to get this vaccine to people before significant cognitive deterioration occurs that could very well be irreversible. There are multiple steps and challenges to getting a vaccine approved and it often takes decades to ensure it’s safe and effective.

Alzheimer’s disease is a far more multifaceted disease than was first supposed. This makes the development of an effective vaccine in humans more complex. The exact underlying pathology of Alzheimer’s disease remains controversial. Some scientists believe a buildup of the tau protein is to blame, while others think another mechanism — such as inflammation — is at play. Despite the considerable progress being made, health experts agree that much more research is needed to better understand the disease in order to develop a safe, effective treatment.