The hunt for Alzheimer’s treatment intensifies

Scientists are racing to find out if a proposed vaccine against Alzheimer’s disease – the most common form of dementia – would actually prevent some of the most prevalent forms of the disease. A…

The hunt for Alzheimer's treatment intensifies

Scientists are racing to find out if a proposed vaccine against Alzheimer’s disease – the most common form of dementia – would actually prevent some of the most prevalent forms of the disease.

A team of research scientists who have spent the last 18 months in collaboration with the University of Oslo are looking at the effects of giving small amounts of vaccine into rodents with Alzheimer’s, and have been quite hopeful about the results to date.

“We didn’t achieve any benefit because we had no control group,” said Dr Margareta Berger, lead researcher on the study, at the Alzheimer’s Disease International (ADI) conference in Washington DC. “However, we have learnt valuable lessons which have encouraged us to keep pushing the development of this therapy forward.”

The trial is one of the many investigations underway worldwide to find effective ways to block the buildup of toxic plaques in the brain, a condition known as “neurofibrillary tangles” and also known as “plaques” and “tangles”, which cause the gradual destruction of cognitive ability.

In this case, the researchers did not get any benefit because they were studying mice that had already developed neurofibrillary tangles and large brain atrophy; researchers use this term to describe the changes in brain tissues that are a typical sign of Alzheimer’s disease, a condition in which the brain experiences atrophy as a result of the protein toxic plaques and tangles. These kinds of brain changes are visible in the hippocampus, the “short branch” of the brain responsible for learning and memory.

However, the researchers – who are part of the Cell Stem Cell Therapeutics Programme – still believe their trial is worthwhile, and are hopeful that the vaccine they are currently developing could one day prevent the loss of brain tissue.

The research team has injected mice with antisense oligonucleotides, a form of RNA which works by specifically targeting the abnormal proteins in a mouse brain. In the brain, these antisense oligonucleotides could prevent the formation of neurofibrillary tangles and large brain atrophy, said Berger.

For now, Berger said the protein levels in the brain of mice that have been injected with the vaccine have remained stable for an extended period of time. “This suggests that if we conduct similar studies in humans, our vaccine should have a similar effect,” she said.

The question of whether or not those mice had some protection against neurofibrillary tangles, and whether this effect would stick after the injection was blocked, is what this group of researchers is now trying to answer.

The new research, being presented at ADI 2018, has received international attention. “Pioneering research using the natural state of oligonucleotides to fight memory loss from Alzheimer’s disease is bringing us ever closer to a therapeutic vaccine,” said Dr Stanley Riddell, chief executive officer of ADI.

There are, of course, still a number of factors to be determined before the injected vaccine could be considered a viable treatment for human dementia. “It’s important for us to study the consequences of inflammatory reactions and these effects will be discussed in more detail at the Alzheimer’s Association International Conference,” said Berger.

Vaccine v vaccine

Professor James Kirkup from the Biochimica & Biomedical Engineering Institute at UCL, said the research is fascinating, but also important for the wider issue of new ways to fight dementia. “It’s important to remember that the ADI study is part of a wider investigation, and that these findings should not be taken as an indication that humans will develop the same results,” he said.

Professor Shane Cavanagh from the University of Edinburgh also welcomed the findings, saying his group in the area of prevention of Alzheimer’s had already published a number of interesting research papers based on injecting a small amount of antibodies into the brain.

“I think this could be a valuable method to try and develop an Alzheimer’s disease vaccine,” he said. “Such a vaccine would most likely be non-toxic as the brain would be treated with an already-existing, neutralising antibody. We are hoping this approach will allow us to develop a ‘proof of concept’ but the results of this trial have, unfortunately, not yet shown that the vaccine is successful in protecting against memory loss in humans.”

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