Researchers at the University at Buffalo and the Institute for Basic Research in Developmental Disabilities are developing a novel immunotherapy approach for Alzheimer's disease, targeting multiple epitopes of amyloid-beta (Aβ) and tau proteins. The experimental vaccine aims to stimulate the immune system to clear or slow the progression of amyloid plaques and neurofibrillary tangles, the two main pathological hallmarks of Alzheimer's.
Targeting Multiple Epitopes for Enhanced Immune Response
Jonathan Lovell, SUNY Empire Innovation Professor in the Department of Biomedical Engineering at UB, leads the research team. Their approach distinguishes itself by targeting multiple epitopes simultaneously, rather than a single one. "By targeting multiple epitopes simultaneously, we aim to train the immune system to recognize and attack these problematic proteins more broadly," Lovell explained. The immunotherapy concept, detailed in the journal Brain, Behavior, and Immunity, suggests the body can mount an immune response to multiple sites within the key polypeptides of both Aβ and tau.
Preclinical Success in Alzheimer's Mouse Models
In collaboration with researchers at the Institute for Basic Research in Developmental Disabilities (IBR), the team demonstrated that the immunotherapy can prevent and reduce Alzheimer's-like changes in mice genetically modified to develop a condition similar to Alzheimer's. The immunotherapy combines epitopes from both Aβ and tau proteins with liposomes, tiny fat bubbles, to enhance vaccine delivery and boost the immune response. "What we’ve found is that the mice that received the immunotherapy early on showed fewer signs of Alzheimer’s-related brain damage and performed better in cognitive tests," Lovell said. "The vaccine appears safe and didn’t cause unwanted side effects."
Addressing a Critical Unmet Need
Nearly 7 million Americans over age 65 are living with Alzheimer’s, and that number is projected to nearly double by the year 2050 as the population continues to age. Cheng-Xin Gong, professor of neuroscience at IBR, emphasized the importance of targeting multiple pathological proteins, given that most Alzheimer's cases are sporadic and have more than one cause. Currently, no FDA-approved active immunotherapies exist that are specifically designed to treat Alzheimer’s disease. Most approved treatments focus on symptom management and offer only modest gains.
Future Directions and Human Trials
The researchers are now testing the vaccine on older mice with the disease to assess its therapeutic potential. "We’re now working to test this active immunotherapy approach in a therapeutic setting," Lovell explains. The team is also working on the logistics of moving the vaccine from mice into human trials, potentially within the next few years. The underlying technology has already been tested in humans in Korea for a COVID-19 vaccine, which could facilitate the translation of the technology. The initial step involves establishing manufacturing standards and improving safety testing before human trials can commence. "Alzheimer’s is such a devastating disease that we need bold solutions to address it," Lovell said.
