New Funding For Innovative Dementia Vaccine Research

New Funding For Innovative Dementia Vaccine Research

Alzheimer’s disease and frontotemporal dementia are devastating disorders that emerge following the buildup of misfolded proteins in the brain. The newest generation of Alzheimer’s therapeutics targets accumulations of the protein amyloid beta with engineered antibodies.

Still, the results could have been more impressive, with some adverse effects, not to mention using engineered antibodies can be prohibitively expensive.

Researchers at Washington University in St. Louis have employed a different approach when designing vaccines to train a person’s immune system to remove these accumulations of amyloid beta and tau proteins.

With a $2.9 million grant from the National Institute on Aging, part of the National Institutes of Health (NIH), researchers Jai Rudra, PhD, an associate professor of biomedical engineering at the McKelvey School of Engineering, and Meredith Jackrel, PhD, an assistant professor of chemistry in Arts & Sciences, will design vaccines that generate anti-amyloid beta and anti-tau antibodies using Rudra’s vaccine platform of peptide nanofibers.

The success rate of this depends on vaccine designs that don’t induce inflammation, as it is a constant challenge for the field to counter the chronic inflammation that comes with age.

Rudra said, “Nanofibers have unique properties that make them attractive for making antibodies to tau and amyloid beta proteins, and they don’t cause inflammation like other adjuvants.”

This suggestion came due to the diverse adverse effects of strong vaccine adjuvants on patients’ health. Instead, Rudra uses a nanofiber platform he developed in previous vaccine research.

Recent trials of dementia treatments, according to Jackrel, have all failed in part because of the brain inflammation that ensues, which is why they are going down a different path with nanofibers. “The noninflammatory nature of these is a good strategy to counter that,” she said.

Jackrel and Rudra will work with WashU Medicine researchers to test their vaccines. Tim Miller, MD, PhD, the David Clayson Professor of Neurology, and Kathleen Schoch, PhD, an assistant professor of neurology, will assist by testing the vaccines on transgenic mice that develop disorders that mimic various dementias in the brain.

“Disaggregating them is going to be very challenging,” said Rudra, noting that it will likely be much easier to attempt to prevent the snowballing of dementia symptoms by nipping all that neuroinflammation in the bud, potentially as early as people are entering middle age.

This also aligns with other initiatives at WashU to develop blood tests for the early detection of various neurodegenerative diseases. Further projects outside biomedical engineering are looking to apply all medical and lifestyle treatments beyond just immune system big guns.

“Dementia and neurodegeneration are not one single disease or stem from one single source, so it will take a multipronged approach,” Jackrel said.