University of New Mexico researchers have received funding to launch an early-stage clinical trial of a vaccine engineered to clear pathological tau protein from the brains of patients suffering from Alzheimer's dementia.
The Phase 1a/1b trial, supported in part by a $1 million grant from the Alzheimer's Association's Part the Cloud initiative, will test the novel vaccine, which was developed by UNM School of Medicine scientists, said Kiran Bhaskar, PhD, professor in the Departments of Molecular Genetics & Microbiology and Neurology.
The primary endpoint of this study is safety and tolerability. Can these subjects take these vaccinations without any anticipated side effects or adverse events? The second endpoint is the immunogenicity – can they make antibodies to tau?"
Kiran Bhaskar, PhD, Professor, Departments of Molecular Genetics & Microbiology and Neurology, UNM School of Medicine
If all goes well, the next step would be a Phase 2 study to assess whether the vaccine – which has shown promising results in rodents and monkeys – is effective in human patients, Bhaskar said.
In a normal brain, the tau protein stabilizes the microtubules that form the "skeleton" of neurons. But when it undergoes a process called phosphorylation, it is ejected from neurons, creating tangles that are characteristic of Alzheimer's and other neurodegenerative diseases.
The FDA has approved several drugs in recent years that reduce levels of amyloid beta, another protein implicated in Alzheimer's pathology, but they barely slow progression of the disease, leading many to wonder whether targeting tau might be a better bet.
The new trial will be conducted under the direction of Janice Knoefel, MD, at the UNM Center for Memory & Aging, which recently won designation as a federal Alzheimer's Disease Research Center. The trial will likely start enrolling participants early in 2026 and is expected to last for 12 months, Bhaskar said.
In the double-blinded study, half the subjects will receive the active vaccine and half will get an inert placebo, he said. Blood tests, antibody tests, cognitive assessments and other biomarkers will be collected at various points during the trial.
UNM scientists created the vaccine by attaching pT181, a region of the altered tau protein that serves as an Alzheimer's biomarker, to a virus-like particle (VLP) platform developed by Bhaskar's colleagues Bryce Chackerian, PhD, and David Peabody, PhD.
VLPs are essentially viruses that have had their genetic material removed, leaving only their outer protein shell. Without a genome, they can't reproduce, but the body's immune system still recognizes them as invaders and manufactures antibodies to attack them – along with the proteins attached to their surface.
In this case, the pT181 protein segment attached to the surface of the VLP has been shown to trigger an immune response, leading to the elimination of the tau tangles in animal study subjects, which also saw improvements in their cognitive performance.
The antibodies from the monkeys bound to the human version of the tau protein. The same thing happened when the monkey sera was exposed to tau in brain tissue from people who had died from Alzheimer's.
But animal models and test tube experiments aren't sufficient to prove that the vaccine will work in human subjects. "The bottom line is, yes, we have some immunological data, and it does seem to do well, but we have to move with caution," Bhaskar said.
The Alzheimer's vaccine will be produced in partnership with TheraVac Biologics, a Canadian biotech company that holds an exclusive license to the technology, Bhaskar said. To receive FDA approval for the study, the vaccine must be produced using the agency's "good manufacturing practices" standard.
Phase 1 clinical studies, the next step after animal research, typically determine whether a drug is safe for humans and help establish the dosage that might be needed to trigger a therapeutic response, Bhaskar said.
Major funding for the trial will be provided by Part the Cloud, an Alzheimer's Association initiative led by California philanthropist Michaela Hoag, who lost both of her parents to the disease.
Through Hoag's efforts, Part the Cloud has raised nearly $90 million since 2012 for research to accelerate translation of laboratory findings through trials into possible therapies – filling the gap in Alzheimer's drug development by providing essential support for early-phase clinical trials.
Bhaskar said his team will need to raise additional funding to pay for the expensive process of manufacturing the vaccine. Grant applications have been submitted in the U.S. and Canada, he said.
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