Renewed hope in Alzheimer's fight with vaccine trials

Clinical trials are in progress for at least seven Alzheimer’s vaccines, with a focus on eliminating beta amyloid or tau proteins. This resurgence follows a setback over two decades ago when a promising vaccine led to severe brain inflammation in some participants. Modern approaches involve highly targeted antibodies, bypassing the immune system's complex machinery.

Eisai and Biogen's Leqembi and Eli Lilly's donanemab are examples of such treatments, reinforcing the strategy of amyloid removal in early-stage Alzheimer's. Companies like Vaxxinity, AC Immune, and Prothena are now exploring vaccine options that aim to stimulate an immune response without excessive inflammation. The FDA has fast-tracked some of these vaccines, expediting their review process.

Dr. Reisa Sperling, a researcher at Mass General Brigham, emphasizes the potential of vaccines in Alzheimer's prevention. She is leading a trial on cognitively normal individuals showing early Alzheimer's markers and is considering using vaccines in future studies. However, the development of Alzheimer's vaccines is still in its early stages and will require extensive trials to prove their efficacy.

A promising candidate, Vaxxinity's UB-311 vaccine, showed safety and tolerability in a Phase 2 trial, with no cases of brain swelling. However, a significant minority experienced brain bleeding, a side effect also observed in infused treatments. Despite challenges, the success of treatments like Leqembi has spurred increased enthusiasm and investment in Alzheimer's vaccine research.

The earlier failures of Alzheimer's vaccines were partly due to an overactive immune response. Current research focuses on targeting B cells, responsible for antibody production, to avoid such complications. Companies like AC Immune and Prothena are developing vaccines targeting both amyloid beta and tau proteins, with the latter also involved in trials for anti-amyloid and anti-tau antibodies. The goal is to generate a strong immune response, especially critical for older individuals with weaker immune systems, and ultimately, to prevent Alzheimer's in its pre-symptomatic stage