A newly published study shows promising results for a new Alzheimer’s vaccine from the pharmaceutical company, Vaxxinity. I am getting very excited about vaccines that are under development for the prevention and treatment of Alzheimer’s disease.
This article will review how the vaccine works for Alzheimer’s disease and the results from the early clinical trials.
What is Alzheimer’s disease?
Before I proceed, it’s important to describe what we currently know about Alzheimer’s disease (AD). It is a chronic neurodegenerative disease that usually starts slowly and worsens over time. It accounts for 60-70% of dementia cases, even though the terms are sometimes used interchangeably. Alzheimer’s disease is a form of dementia.
Amyloid plaques (caused by amyloid beta, or Aβ), phosphorylated tau tangles (pTau), and neurofibrillary tangles are generally easily visible pathologies that can be observed by microscopic analysis of brain tissue from autopsies of those potentially afflicted by AD. These plaques and tangles seem to affect nerve functioning. Despite these observations, the precise pathophysiology, or development, of the disease is not known.
Since amyloid plaques are often identified in patients with Alzheimer’s disease, a large amount of research is focused on attacking those plaques as a way to reverse the effect on nerves which leads to AD.
The causes of AD are unknown (notice how much we do not know about this disease), although it is speculated that it is mostly genetically related, with a large number of genes that underlie this relationship.
And since we have no clear understanding of the etiology and pathophysiology of AD, there are no effective treatments available today for the disease, although there are some drugs that target the amyloid plaques but have not been shown to change the course or outcomes of AD.
There are a couple of medications that help manage some of the symptoms of the disease, but they are certainly not cures. There are several drugs at the very earliest stages of development that may hold out hope to treat the underlying disease.
One more thing that needs to be made clear. There are no biological tests for Alzheimer’s disease — usually, you can only find the amyloid plaques and other pathologies in post-mortem autopsies. Unfortunately. in the absence of an autopsy, clinical diagnoses of AD are “possible” or “probable”, based on other findings, such as memory tests and other methods.
In the United States, about 10.7% of seniors (≥65 years) currently have Alzheimer’s dementia, and this proportion is expected to grow with the aging population. The economic burden of AD is expected to surpass $2.8 trillion by 2030.
Vaxxinity Alzheimer’s disease vaccine
Vaxxinity, a Florida-based vaccine development company that is researching a number of innovative vaccines, is investigating the UB-311 vaccine candidate for treating Alzheimer’s disease. UB-311 is an immunotherapeutic vaccine that targets toxic forms of aggregated amyloid-beta in the brain to treat Alzheimer’s disease.
UB-311 is a synthetic peptide-based active immunotherapy vaccine that targets amyloid beta. The vaccine is very similar to standard vaccines that present an antigen, in this case, a synthetic peptide that appears similar to amyloid beta proteins, that “trains” the immune system to attack and destroy the amyloid beta. I am oversimplifying this vaccine’s technology since it’s quite a bit more complex than what’s found in most standard vaccines.
The end effect of this vaccine is that it would destroy the amyloid beta proteins, thereby potentially reducing the effects of the protein on the nervous system, which should either “cure” or at least, reduce the effects of Alzheimer’s disease.
UB-311 early results
In a paper published in August 2023 in EBioMedicine, lead researcher Hui Jing Yu led a team that set up a 78-week, randomized, double-blind, placebo-controlled, parallel-group, multicentre, phase 2a study that was conducted in Taiwan. The 43 participants were randomized in a 1:1:1 ratio to receive seven intramuscular injections of UB-311, five doses of UB-311 with two doses of placebo (Q6M arm), or seven doses of placebo (placebo arm).
Here are the key results:
- A 97% antibody response rate was observed and maintained at 93% by the end of the study across both UB-311 arms. This means that the vaccine induced an immune response against amyloid beta.
- The vaccine was considered safe with only minor adverse events, typical of most vaccines.
Summary
It’s important to note that this is a very early clinical trial, at phase 2A, and that we are a long way from clear results from a large phase 3 clinical trial. Furthermore, this study only showed that the participants had an immune response to amyloid beta, but did not show whether there was an actual decrease in the amount of amyloid beta.
Furthermore, this study did not show whether the immunotherapy reduced symptoms of Alzheimer’s disease, let alone cure it. But, this will be an endpoint of the phase 3 clinical trial, so I’m hopeful.
For now, Vaxxinity has an interesting and potentially game-changing vaccine candidate for Alzheimer’s disease. Within a few years, we may have the ability to prevent, treat, and potentially reverse Alzheimer’s disease.
Citations
- Wong W. Economic burden of Alzheimer disease and managed care considerations. Am J Manag Care. 2020 Aug;26(8 Suppl):S177-S183. doi: 10.37765/ajmc.2020.88482. PMID: 32840331.
- Yu HJ, Dickson SP, Wang PN, Chiu MJ, Huang CC, Chang CC, Liu H, Hendrix SB, Dodart JC, Verma A, Wang CY, Cummings J. Safety, tolerability, immunogenicity, and efficacy of UB-311 in participants with mild Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase 2a study. EBioMedicine. 2023 Aug;94:104665. doi: 10.1016/j.ebiom.2023.104665. Epub 2023 Jun 29. PMID: 37392597; PMCID: PMC10338203.
