A vaccine to ward off dementia is currently being readied for human clinical trials after successful testing in a variety of animal models. A joint Californian and Australian research team supported by the US National Institutes for Health is looking to use immunotherapy to treat Alzheimer’s, having designed synthetic vaccines that target the abnormal accumulations of both beta amyloid and tau proteins seen in the brains of patients with Alzheimer’s disease. The work is described in a new paper in the journal Alzheimer’s Research & Therapy that describes the latest animal studies with this vaccine, with medical researchers at the Institute for Molecular Medicine and University of California, Irvine (UCI) collaborating with Professor Nikolai Petrovsky, the research director of biotechnology company, Vaxine Pty Ltd, based in Adelaide, Australia and Professor at Flinders University.
The latest research tested the ability of a vaccine to remove accumulated beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which together lead to neurodegeneration and cognitive decline in Alzheimer’s disease. Alzheimer’s disease (AD) is the leading cause of age-related dementia, affecting about 5.7 million people in the US. Major challenges in AD include the lack of effective treatments, reliable biomarkers, or preventive strategies.
Professor of the Institute for Molecular Medicine, Anahit Ghochikyan and colleagues, Associate Professors Hvat Davtyan and Mathew Blurton-Jones from UCI, and other co-authors tested the universal MultiTEP platform-based AD vaccine formulated with Advax™ adjuvant developed by Professor Petrovsky. The new vaccine was then tested in bigenic mice which exhibit a mixture of Aβ and tau pathologies, thereby mimicking human AD. The vaccine was demonstrated to slow the accumulation of Aβ and tau molecules in the brain of the bigenic mice and delay memory loss. Following on from these successful studies, this vaccine is being readied for human clinical trials which are expected to commence once all manufacturing and regulatory requirements are met, which is anticipated to take about two years.
Professor Petrovsky says the Advax adjuvant method is a pivotal system to help take the combination MultiTEP-based Aβ/tau vaccines therapy, as well as separate vaccines targeting these pathological molecules, to clinical trials – perhaps within two years.
“Our approach is looking to cover all bases and get past previous roadblocks in finding a therapy to slow the accumulation of Aβ/tau molecules and delay AD progression in a the rising number of people around the world,” says Professor Petrovsky, who will work in the US for the next three months.
The Alzheimer’s field is littered with unsuccessful drug candidates that failed in late stage clinical trials so the search for new preventions or therapies continues. A recent report on a human monoclonal antibody, aducanumab, that just targets A showed that high dose of this antibody reduced clinical decline in patients with early AD as measured by primary and secondary endpoints, and aducanumab has been submitted to the FDA for consideration for approval as an AD therapy. However, monoclonal antibody treatment would likely frequent (monthly) administration of high concentrations of antibody for life, making it both highly expensive as well as impractical. By contrast the new combined vaccination approach that targets both A and tau, could potentially only require 3 to 4 initial immunizations followed by periodic annual boosters, making it potentially much less expensive and more practicable than monoclonal antibody therapy.
‘Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice‘ (2019) by H Davtyan, A Hovakimyan, SK Shabestari, T Antonyan, MA Coburn, K Zagorski, G Chailyan, I Petrushina, O Svystun, E Danhash, N Petrovsky, DH Cribbs, MG Agadjanvan, M Blurton-Jones and A Ghochikyan, has been published in Alzheimer’s Research & Therapy (BMC, Springer Nature).