Photo credit: www.sciencedaily.com
Researchers at the University of New Mexico Health Sciences are embarking on a promising initiative to develop a vaccine aimed at preventing the accumulation of pathological tau, a protein linked to Alzheimer’s disease. Human clinical trials are anticipated to commence soon, following exciting developments in their research.
A recent study published in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association outlines findings from a team spearheaded by Dr. Kiran Bhaskar, a professor within the Department of Molecular Genetics & Microbiology at the UNM School of Medicine. The study demonstrates that an experimental vaccine has elicited a robust immune response in both mouse models and non-human primates, furthering the team’s previous work in this area.
Dr. Bhaskar highlighted the significance of these results: “The efficacy demonstrated in non-human primates indicates that we are nearing the stage where we can initiate clinical trials,” he stated. To move forward, he and his team are actively pursuing funding support from venture capitalists and the Alzheimer’s Association to initiate Phase 1 trials in human subjects.
Tau is a protein essential for stabilizing neurons; however, its dysfunction leads to abnormal phosphorylation, resulting in the release of malformed tau into the extracellular space. This process contributes to the formation of neurofibrillary tangles, a hallmark of Alzheimer’s and various neurodegenerative conditions.
While several FDA-approved therapies exist that target amyloid beta, another protein implicated in Alzheimer’s, the effectiveness of these treatments has been limited, prompting researchers to consider targeting tau as a potentially more effective strategy.
The immunotherapy developed at UNM specifically targets antibodies that attach to pT181, a segment of the altered tau protein characterized as a biomarker for Alzheimer’s. In past studies, published in 2019 in NPJ Vaccines, the team found that administering the vaccine to mice genetically modified to develop pathological tau resulted in the production of antibodies, a reduction in the severity of tau tangles in critical brain areas, and improved cognitive test performance.
The current study builds upon these initial findings. The vaccine sparked a vigorous immune response in additional strains of mice engineered to develop tau-related diseases, including one strain containing a human tau gene. Collaborating with the University of California, Davis, and the California National Primate Research Center, the team reported similar immune responses in macaques, primates that share closer physiological similarities to humans.
Moreover, the antibodies developed from the vaccinated monkeys were tested against blood plasma samples from individuals with mild cognitive impairment, a condition that can precede Alzheimer’s dementia. The antibodies were found to effectively bind to the human variant of the tau protein, providing further evidence of the vaccine’s potential efficacy.
The vaccine employs a virus-like particle (VLP) platform created by Dr. Bryce Chackerian and Dr. David Peabody from the Molecular Genetics & Microbiology team. VLPs resemble viruses but lack viral DNA, rendering them non-harmful. This platform allows for the attachment of protein fragments like pT181 to the surface, making them identifiable to immune cells.
Bhaskar noted that VLP vaccines can induce long-lasting immunity with just one primary dose followed by two booster shots. Significantly, they do not require additional substances, known as adjuvants, which are often used to amplify immune responses. Their safety profile has already been confirmed in human trials.
Dr. Nicole Maphis, a postdoctoral researcher in the UNM Department of Neurosciences and the lead author on both studies, emphasized the importance of the collaboration with UC Davis for validating the vaccine’s efficacy. “This partnership is crucial because it widens our research into a model that is closer to human physiology,” she explained. “Mice have a different immune response, but these non-human primates offer insights that are significantly more relevant to human health.”
Source
www.sciencedaily.com