New mRNA method targets Tau Protein in Alzheimer’s disease

Researchers at The Florey Institute have developed a novel method using mRNA technology to specifically target the harmful tau protein, which accumulates in the brains of dementia patients, including those with Alzheimer’s disease.

mRNA technology has primarily been used in vaccines, particularly those designed to combat COVID-19. However, The Florey’s new research, published in Brain Communications, positions the institute as a major leader in mRNA technology. Dr. Rebecca Nisbet is leading this new direction in technology.

“This is the first instance where mRNA has been investigated for potential use in Alzheimer’s disease,” said Dr. Nisbet. “Our findings in cell models show that mRNA technology has applications beyond vaccine development.”

Dr. Nisbet likened mRNA to an instructional manual for cells. “Once inside the cell, the mRNA is read, and the cell produces an antibody.”

The Florey team used mRNA to direct cells in models to produce RNJ1, an antibody developed by Dr. Nisbet to target tau, a protein that forms clumps in the brain cells of dementia patients.

“To our knowledge, this is the first time a tau antibody has been able to directly interact with tau inside the cell,” Dr. Nisbet explained.

PhD student Patricia Wongsodirdjo, the first author of the paper, commented, “Our approach can be applied to any therapeutic antibody, and we believe that by combining this strategy with nanoparticle packaging, we can improve the targeting of toxic molecules in the brain and enhance patient outcomes compared to traditional methods.”

Dr. Nisbet noted that further research is needed on RNJ1. While emerging Alzheimer’s treatments like lecanemab show promise, they are costly to produce and do not efficiently deliver an active antibody into brain cells.

“Conventional antibodies like lecanemab can remove some harmful plaques outside brain cells but cannot reach toxic proteins like tau, which are inside our brain cells,” Dr. Nisbet explained.