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Antonia Nicole Klein’s research developing a drug to treat and maybe one day help prevent Alzheimer’s disease has received two years of funding from a prestigious research foundation. Klein, who works with Sabine Gilch, assistant professor and Tier II Canada Research Chair in Prion Disease Research in the Faculty of Veterinary Medicine, has been awarded the German Research Foundation (DFG) research fellowship.

“Antonia is passionate about her Alzheimer’s research,” says Gilch. “The fellowship gives her some independence and makes her more competitive if she decides to start her own research group and has to apply for funding as a principal investigator.”

Trying to block a toxic interaction in the brain

Klein is looking at Amyloid-beta peptides — the main component of the plaque that’s found in the brains of people who have died with Alzheimer's disease. “A high concentration of Aβ oligomers, an aggregated form of Abeta, is toxic for brain cells — they destroy the brain,” she says. The mechanism by which Aβ oligomers kill brain cells may be through interacting with cellular prion proteins (PrPC).

“From work of other groups, we know that the interaction between the cellular prion with Aβ oligomers starts the toxicity,” she says. “So maybe if we can stop them from interacting, there’ll be no toxicity.” Klein is using peptide aptamers — amino acids integrated in a scaffold protein — to bind with PrPC and therefore inhibit the interaction between Aβ oligomers and PrPC and prevent brain cells from dying.

“We have these peptide aptamers and they bind to cellular prion proteins at the spot Aβ oligomers normally bind. When this position is blocked, Aβo can no longer bind, and there’s no toxic signal anymore,” says Klein, who studied Alzheimer’s for her PhD in Germany from 2012 to 2015.

She is testing different peptide aptamers to identify which one is the most effective at binding. “I want to find one which is good and can really show the effect we want to see,” she says. Eventually the peptide aptamers could be tested on animal models and if proven effective with mice, taken to human trials.

Alzheimer's is one of six leading causes of death in U.S.

There are no current therapies to treat Alzheimer’s disease, which affects the central nervous system and accounts for as much as 80 per cent of dementia cases. “Alzheimer’s is one of the six leading causes of death in the U.S.,” says Klein. “We are getting older and older and even more people will get this disease. There is no cure right now. I’m trying to find a drug for Alzheimer’s.”

Her project is also supported by funds from the Alberta Prion Research Institute and the Alzheimer Society of Alberta and Northwest Territories.