Possible dementia vaccine closer after mice studies
Human trials tipped within two years
December 31, 2019
Science Daily/Flinders University
A vaccine to ward off dementia may proceed to clinical trials after successful animal testing. The research is looking to develop effective immunotherapy via a dual vaccine to remove 'brain plaque' and tau protein aggregates linked to Alzheimer's disease. It is showing success in begenic mice models, supports progression to human trials in years to come.
A preventive treatment for dementia may proceed to clinical trials after successful animal testing.
The US-led research is looking to develop effective immunotherapy via a new vaccine to remove 'brain plaque' and tau protein aggregates linked to Alzheimer's disease.
Recent success in bigenic mice models supports progression to human trials in years to come, the researchers say.
A new paper in the journal Alzheimer's Research & Therapy paves the way for more work in 2020, with medical researchers at the Institute for Molecular Medicine and University of California, Irvine (UCI) working with a successful vaccine formulated on adjuvant developed by Flinders University Professor Nikolai Petrovsky in South Australia.
The latest research aims to come up with a new treatment 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 vaccines formulated in the adjuvant developed at Professor Petrovsky's Australian lab.
The possible new therapies were tested in bigenic mice with mix Aβ and tau pathologies.
"Taken together, these findings warrant further development of this dual vaccination strategy based on the MultiTEP technology for ultimate testing in human Alzheimer's disease," the lead authors Professor Ghochikyan and Blurton-Jones conclude.
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.
Several promising drug candidates have failed in clinical trials so the search for new preventions or therapies continues.
A recent report on human monoclonal antibody, aducanumab, showed that high dose of this antibody reduced clinical decline in patients with early AD as measured by primary and secondary endpoints.
However, it is obvious that it could not be used as a preventive measure in healthy subjects due to the need for frequent (monthly) administration of high concentrations of immunotherapeutic.
Professor Ghochikyan says there is a pressing need to keep searching for new preventive vaccine to delay AD and slow down progression of this devastating disease.
The new combined vaccination approach could potentially be used to induce strong immune responses to both of the hallmark pathologies of AD in a broad population base of vaccinated subjects with high MHC (major histocompatibility complex) class II gene polymorphisms, the new paper concludes.
https://www.sciencedaily.com/releases/2019/12/191231111835.htm
Dementia study reveals how proteins interact to stop brain signals
December 10, 2019
University of Edinburgh
Fresh insights into damaging proteins that build up in the brains of people with Alzheimer's disease could aid the quest for treatments.
A study in mice reveals how the two proteins work together to disrupt communication between brain cells.
Scientists observed how proteins -- called amyloid beta and tau -- team up to hamper key genes responsible for brain messaging. By changing how genes are expressed in the brain, the proteins can affect its normal function.
These changes in brain function were completely reversed when genetic tools were used to reduce the presence of tau, researchers at the University of Edinburgh found.
The study focused on the connection points between brain cells -- known as synapses -- that allow chemical and electrical messages to flow and are vital to healthy brain function.
Stopping the damage that the two proteins cause to synapses could help scientists prevent or reverse dementia symptoms, the researchers say.
In both the mouse model and in brain tissue from people with Alzheimer's disease, the team found clumps of amyloid beta and tau proteins in synapses.
When both amyloid beta and tau were present in the brain, genes that control the function of synapses were less active. And some of the genes that control the immune system in the brain were more active.
Related to increased immune system activity, the scientists observed immune cells called microglia containing synapses in the brains of mice. This adds to findings from recent studies suggesting that these immune cells consume synapses during Alzheimer's disease.
Alzheimer's disease is the most common form of dementia, affecting some 850,000 people in the UK -- a figure predicted to rise to more than one million by 2025. It can cause severe memory loss and there is currently no cure.
Lead researcher, Professor Tara-Spires Jones of the UK Dementia Research Institute at the University of Edinburgh, said: "More work is needed to take what we've learned in this study and find therapeutics -- but this is a step in the right direction, giving us new targets to work towards."
The study is published in the journal Cell Reports. It was funded by the European Research Council, and the UK Dementia Research Institute which is funded by the UK Medical Research Council, Alzheimer' Society and Alzheimer's Research UK.
https://www.sciencedaily.com/releases/2019/12/191210111726.htm