Some of the most common indicators of Alzheimer’s disease include build-ups of beta-amyloid plaques, tau proteins, and neuroinflammation. These are the targets for a vaccine against Alzheimer’s progression. One of the simpler methods to vaccine development is repurposing approved therapeutics, and it is estimated that up to 39% of Alzheimer’s interventions comprise repurposed therapeutics.
Currently the FDA has not authorised preventative vaccines but there are candidates for consideration. Several of these are in Phase II or III trials with approval anticipated over the next10 years. As the sixth leading cause of death in the United States, Alzheimer’s isn’t going to wait for this process to be completed.
Derek Lowe, writing in Science in 2021 stated that it was important to be cautious of suggestions that “pandemic-driven changes” were enabling further developments towards an Alzheimer’s vaccine. He explores several steps towards this end, such as the “discovery of a pseudo-beta-hairpin structure” in a region of the beta-amyloid protein and how it could be turned into a “stabilised, truncated form” in a vaccine antigen. The risk of the antibody becoming trapped in the plaques themselves, causing inflammatory toxicity in previous approaches, is reduced.
Another step he considers is a nasally administered vaccine candidate with Protollin as the active ingredient. Although initially developed as an adjuvant, Protollin demonstrated significant immunostimulatory effects in mice. Lowe reports that as anti-amyloid antibodies are not formed, “hopes that some of the side effects in the anti-amyloid-antibody world can be sidestepped”.
In January 2022 early human trials of nasally delivered Protollin began. The hope is that in up to 5 years an application for FDA approval can be made. With an estimated 5.8 million people in the US having the disease or related dementias, it’s more important than ever to push this forward.