Fruit flies and test tubes open new window on Alzheimer’s disease

They found that in test tube studies the molecule not only prevents the protein from forming clumps but can also reverse this process. Then, using fruit flies with Alzheimer’s disease, they showed that the same molecule effectively "cures" the insects of the disease.

Alzheimer’s disease is the most common neurodegenerative disorder linked to protein misfolding and aggregation, or clumping. Previous studies in animal models have shown that clumping of a protein known as the Alzheimer beta (A-beta) peptide causes memory impairment and cognitive deficits similar to those in patients with Alzheimer’s disease. When these clumps of protein are deposited in the brain they damage neurones (brain cells), although the mechanism involved is still not understood.

The new molecule – designed by scientists in Sweden – is a small protein known as an Affibody (an engineered binding protein). In this new study, researchers at the University of Cambridge and the Swedish University of Agricultural Sciences found that in test-tube experiments this protein binds to the A-beta peptide, preventing it from forming clumps and breaking up any clumps already present.

In a second experiment, they studied the effect of this Affibody in a Drosophila (fruit fly) model of Alzheimer’s disease previously developed at Cambridge. Working with fruit flies that develop the fly equivalent of Alzhiemer’s because they have been genetically engineered to produce the Abeta protein, they crossed these flies with a second line of flies genetically engineered to produce the Affibody.

They found that offspring – despite producing the A-beta protein – did not develop Alzhiemer’s.

"Flies are our first ‚biological test bench’for this new type of medicine. We wanted to know if it was at all possible to prevent the effects of the A-beta protein in the brain of a living organism", says Professor Torleif Härd, SLU.

"But the results are positive and we think we now how this molecule can be further developed to function as a medicine, although it is not possible to say how long this will take, or if it is possible to treat patients who have already developed the disease. The next step will be performing tests on mice."

The research will continue in collaboration with KTH and the biotech enterprise Affibody AB, Stockholm. The study is published in PLoS Biology.

More information:Professor Torleif Härd, SLU; torleif.hard@molbio.slu.se, +46-18 471 40 55

Pressofficer Carin Wrange: +46-70 247 84 22; Carin.Wrange@adm.slu.se
(idw, 03/2010)

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