Alzheimer’s vaccine targets early and later disease stages

Researchers in the United States and Australia are working together to develop a vaccine that they believe could have both preventive and therapeutic effects on Alzheimer’s disease.

The vaccine, detailed in a study titled, “Alzheimer’s disease Advax^CpG- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules,” and published in Nature’s Scientific Reports journal, targets two types of proteins involved in early and late pathogenesis of Alzheimer’s disease.

Alzheimer’s disease is an irreversible, progressive brain disease affecting nearly 46 million people across the globe. Often manifesting after age 60, the disease inhibits memory and cognitive skills, making even simple tasks difficult, according to the National Institute on Aging (NIA).

Researchers at Flinders University in Australia, the University of California-Irvine and the Institute of Molecular Medicine-a California non-profit aimed at fighting chronic diseases-are studying a vaccine to fight Alzheimer’s disease by inducing antibodies against both aggregated β-amyloid (Aβ) and Tau proteins, helping to remove them from the brain and restore normal brain function, said Nikolai Petrovsky, PhD, director of endocrinology at Flinders Medical Centre and professor of medicine at Flinders University.

“It is different from previous vaccines in that it is between 100 and 1,000 times more potent at antibody induction than previous versions,” Petrovsky told Medical Economics. “This is critical to vaccine success as we now know that very high levels of antibodies are required for protection and this likely explains the failures of previous generations of vaccines.”

Next: Vaccine for early intervention

Vaccine proposed for early intervention and alter therapeutic use

Scientists agree that the Aβ and tau proteins are the optimal targets for Alzheimer’s disease immunotherapy, although how the two proteins work as the disease progresses is still debated.

“Therefore, we propose that anti-Aβ immunotherapy should be initiated at the early stages of [Alzheimer’s] to minimize synaptic and neuronal loss, while anti-tau immunotherapy may be most effective when disease progression is more advanced,” researchers state in the study. “Thus we have decided to generate vaccines that will target pathological molecules either sequentially (e.g. Aβ vaccinations followed by tau vaccination) or simultaneously (mixture of Aβ plus tau vaccines, or dual-epitope vaccine containing both Aβ and tau B cell epitopes).”

The researchers also added an adjuvant to the vaccine to enhance immune responses using memory Th cells previously generated in response to infection or vaccination. This approach may be especially beneficial in elderly patients since it uses memory T cells instead of naïve T cells, which decrease in number during the aging process.

The formation of Aβ-mediated plaques is believed to be the primary event in the development of Alzheimer’s disease. Later in the disease, Alzheimer’s becomes self-propagating with less dependence on Aβ in favor of other proteins, including Tau. As a result, researchers believe vaccines targeting only Aβ proteins may only be effective in early Alzheimer’s, while those affecting tau may work better in later stages. Therefore, researchers concluded that a vaccine combining both proteins may be more effective across the spectrum of Alzheimer’s development and progression.

Next: Primary care concerns

Primary care concerns

Petrovsky said primary care physicians should realize that while there are no good treatments for Alzheimer’s disease currently, vaccines and monoclondal antibodies are showing promise in reversing the disease. The hope, he said, is that the vaccine can be used both to prevent Alzheimer’s disease, as well as to treat the disease in those already suffering from its effects.

The vaccine is still at least 7 or 8 years away from hitting the market, Petrovsky said, adding that he hopes to enter Phase 1 clinical trials within the next 2 years.

Estimates rank Alzheimer’s as the sixth leading of death and the most common cause of dementia. The root causes of the disease vary, and mixed causes-including Lewy body dementia, frontotemporal disorders and vascular dementia-are common, according to NIA.

The primary clinical features of the disease are amyloid plaques and neurofibrillary-or tau- tangles. Neurons also suffer damage, with the connection between neurons and different parts of the brain being lost, resulting in a loss of signals between the brain and various functions of the body.

Changes in the brain can start a decade or more before the noticeable changes in memory or function manifest. By the later stages of the disease, brain tissue decreases significantly, making those who suffer from the disease completely dependent on others to perform basic activities of daily living.