Vaccines are arguably one of the greatest inventions of medical science of all time. Now, researchers are looking to take vaccine technology one step further to protect against neurodegenerative diseases like dementia. In this Special Feature, we asked experts about what is currently under development, how a dementia vaccine would work, and how quickly we may see one becoming available to the public.
Dementia is an umbrella term referring to a range of disorders that affect the way in which a person’s brain works, causing symptoms including memory loss, behavior changes, and difficulty speaking and walking.
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, there is currently no cure for Alzheimer’s disease or most cases of dementia.
Researchers are now looking at the possibility of protecting a person from developing dementia through a vaccine.
“More and more, there’s an appreciation of the immune system being relevant in the central nervous system, both in terms of driving a disease state, but also potentially recovering from or even preventing a disease from happening, including something as complex and devastating as dementia,” said Dr. David A. Merrill, a psychiatrist, and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center in Santa Monica, CA.
He gave the example of recent evidence showing a person getting the flu or pneumonia vaccine might decrease their risk of developing dementia.
“It’s spurring the idea ‘could immune system activation or support actually help stave off the dementing process or nerve degenerative disease process?’,” Dr. Merrill continued.
“The starting point of the theories or hypotheses about Alzheimer’s didn’t start with ideas about the immune system, but it’s ending up that perhaps the treatments can and should involve helping or addressing immune system function with aging,” he told us.
According to Dr. Michael G. Agadjanyan, vice president and professor of immunology at The Institute for Molecular Medicine in Huntington Beach, CA, 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.
Dr. Heather Snyder, vice president of medical and scientific relations for the Alzheimer’s Association, said it is an exciting time in Alzheimer’s disease research, with over 100 potential therapies being tested at various stages of the research process, and many more being developed.
“There has been some research exploring active immunization, such as vaccines, to ‘protect’ individuals from Alzheimer’s,” she detailed. “These are vaccines that are being developed to target the biology related to Alzheimer’s.”
“They are, in some cases, leveraging the biology of decades of vaccine-related development more broadly in medical care. There are also different types of delivery systems and different types of biology that may be targeted with a vaccine for a potential therapy,” she explained.
Dr. Agadjanyan explained that dementia vaccines would generate immune responses against pathological molecules in the body associated with dementia, including:
- beta-amyloid proteins — toxic build-up of these proteins in the brain is often linked to Alzheimer’s disease
- tau — a protein that helps stabilize the internal structure of neurons in the brain; abnormal tangles of tau protein in the brain are associated with Alzheimer’s disease
- alpha-synuclein — a protein in neurons associated with Parkinson’s disease and Lewy body dementia when large amounts accumulate.
“In Alzheimer’s disease, the following processes develop in the brain tissues,” Dr. Agadjanyan explained to Medical News Today.
“[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,” he said.
“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, etc. — go with them,” he continued. “After a person receives a diagnosis of Alzheimer’s disease, they rarely manage to spend more than five to seven years in this world.”
Dr. Agadjanyan said that current scientific data suggest that 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.
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.
Earlier this year, pharmaceutical company Vaxxinity announced it had received FDA fast-track designation for its immunotherapeutic vaccine for Alzheimer’s disease. The vaccine candidate, UB-311, has completed phase 1 and 2A clinical trials, with phase 2B expected to begin in late 2022.
Dr. Snyder reported that the Alzheimer’s Association’s Part the Cloud program is currently funding an early-phase clinical trial testing the use of a vaccine in reducing brain inflammation in individuals with early Alzheimer’s disease. She stated that the trial is expected to finalize in fall 2023.
And Dr. Agadjanyan is part of a team at The Institute for Molecular Medicine (IMM) developing a vaccine for Alzheimer’s disease.
“Our goal was to develop an immunogenic vaccine that can induce a sufficient level of antibodies in the periphery of all vaccinated cognitively unimpaired elderly with immunosenescence and delay/ halt the onset of Alzheimer’s disease,” he explained.
“We have developed a unique type of vaccine based on the universal platform technology MultiTEP, which we developed at IMM. This platform stimulates memory and naive T helper cells, which in turn activate B cells to produce antibodies at a much higher rate — up to 10 times — than vaccines currently used in clinical trials. With a large number of produced antibodies, the goal is to prevent/suppress the aggregation of [beta-amyloid] and/ or tau and stop or at least delay the onset of the disease.”
– Dr. Michael G. Agadjanyan
When will a dementia vaccine be available?
Dr. Merrill predicted it will be a while before any vaccines are available to the public.
“It’s still going to be a number of years before any vaccine is able to get through the development process, the regulatory hurdles, [and] the phases of clinical trials,” he pointed out.
Dr. Snyder agreed, and stated that the studies to date have been very small or in mice.
“More research in large, diverse human populations are needed before we can comment on the potential usefulness of a vaccine for protecting against or treating Alzheimer’s,” she advised.
Additionally, Dr. Merrill said people may be hesitant towards a dementia vaccine depending on how long the vaccination process may take.
“If you look at the early stage trials, the scheduling or the dosing of the vaccines can be quite variable,” he detailed. “In concept, you might hope for just a single dose vaccine and you would be protected, but the reality may be it might take a series. Monthly vaccination shots for a year is one design.”
“And the question is how interested will people be in getting this?” Dr. Merrill asked. “Clearly, if it truly protects and prevents you from getting Alzheimer’s, I think people would line up and would be very interested. But it’s all in the development of this — this is where it’s uncertain.”
Will dementia vaccines really work?
On the other side of the dementia vaccine argument is Dr. Karl Herrup, professor of neurobiology at the University of Pittsburgh School of Medicine.
He told MNT the dementia vaccines attempt to harness the power of the immune system to fight the biology of dementia and are all based on the hypothesis that deposits of misfolded proteins — amyloid, tau, and others — are the root causes of the disease.
“The vaccines, though differing in their strategies, are all based on using antibodies to the deposits to deplete and/ or remove them,” he explained.
“The bad news is that despite this biochemical success there is no meaningful clinical benefit to the therapies. Indeed in some trials, people on the drug actually fared worse than those on placebo. Many of us, myself included, have long argued that the hypothesis of aggregate-caused dementia rests on shaky grounds,” said Dr. Herrup.
“For us, the results were a bitter disappointment,” Dr. Herrup added. “I would rather be wrong and have a useful Alzheimer’s disease therapy than be right and have to have millions of people continue to suffer, but the results were not surprising.”
Dr. Herrup said that, in his opinion, the only important question about a dementia vaccine or treatment, for that matter, is whether the treatment slows or stops the clinical symptoms of the disease — cognitive decline and behavioral symptoms.
“I predict that none of these therapies will meaningfully alter the disease course,” he continued. “Sadly, since the industry poured most of its resources into these approaches, ignoring or sometimes repressing other avenues of investigation, it will be years before any meaningful therapies are available. For now, the best approaches are non-pharmacological.”
By Corrie Pelc
Fact checked by Ferdinand Lali, Ph.D.