Unlocking how to use mRNA to target Alzheimer's disease

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Graphical summary. debt: brain communication (2024) DOI: 10.1093/braincomms/fcae100

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Graphical summary. debt: brain communication (2024) DOI: 10.1093/braincomms/fcae100

Scientists at The Florey have developed an mRNA technology approach to target tau, a toxic protein that forms in Alzheimer's disease and other dementia patients.

To date, mRNA has been used mainly for vaccines, including those used to fight Covid-19.

New research published in brain communication Establishing TheFlory as a major player in the mRNA field, Dr. Rebecca Nisbett is taking the technology in a new direction.

„This is the first time that mRNA has been studied for use in Alzheimer's disease,” said Dr. Nisbett. „Our work in cell models demonstrates that this technology can serve purposes other than vaccine development.”

He compared mRNA to an instruction manual for cells.

„Once delivered to the cell, the cell reads the mRNA and produces an antibody.”

To target tau, a protein that clumps together in the brain cells of dementia patients, Dr. Florey's team used mRNA to instruct cells in cell models to make RNA1, the antibody that Nisbet developed.

„This is the first time, to our knowledge, that a tau antibody has been able to directly engage tau inside a cell.”

The article's first author, Ph.D. student Patricia Wongsodirtjo, „Our technique can be applied to any therapeutic antibody, and we hypothesize that this strategy, when combined with nanoparticle packaging, will improve targeting of toxic molecules in the brain and improve patient outcomes compared to conventional strategies.”

Dr. Nisbett said RNJ1 still needs more research.

He said emerging Alzheimer's treatments such as lecanemab, approved in the US and under consideration in Australia, are promising but expensive to manufacture and not an efficient way to get the active antibody into brain cells.

„With conventional antibodies like leganemab, small amounts of antibodies that enter the brain can remove some of the harmful plaque outside our brain cells, but cannot access toxic proteins like tau that reside inside our brain cells.” Dr. Nisbet said.

More information:
Patricia Wongsodirtjo et al., An mRNA-Tagged Antibody Approach to Extracellular and Intracellular Tau, brain communication (2024) DOI: 10.1093/braincomms/fcae100

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brain communication

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