Affibody: Unexpected Discovery Made by Swedish Researchers within the Field of Alzheimer: Newly Discovered Protein Inhibits the Formation of the Precursor to Alzheimer’s Plaques.

Non-Regulatory

March 27, 2008

STOCKHOLM, Sweden, March 27, 2008. As of today, there is no cure or effective treatment of Alzheimer’s disease. Swedish researchers have now through their discoveries opened up new possible strategies for potential treatment of the actual cause of the disease. These results have been obtained through a fruitful collaboration between researchers from Sahlgrenska Academy at University of Gothenburg, Royal Institute of Technology (Kungliga Tekniska Högskolan, KTH) and the company Affibody AB.

The researchers have for the first time shown how a newly developed Affibody® molecule, with specific binding affinity for the Alzheimer’s amyloid-ß peptide, can stabilize and encapsulate the ß-peptide.

In Alzheimer’s disease, toxic aggregates of the amyloid-ß peptide assemble in the brain as fibrils and eventually plaques. The discovery gives insights on how the toxic aggregates are formed and how this process might be inhibited. These results are now published in the distinguished journal, Proceedings of the National Academy of Sciences of the USA*.

A research group at Sahlgrenska Academy at University of Gothenburg, headed by Professor Torleif Härd has determined the three-dimensional structure of the amyloid-ß peptide, by the use of the Affibody® molecule that can specifically capture the ß-peptide. Furthermore, it has been shown that the Affibody® molecule stabilizes the ß-peptide and inhibits the ß-peptide from forming the toxic aggregates known as a precursor of Alzheimer’s disease.

“It feels really rewarding when our research on the Affibody® technology platforms leads to breakthroughs of unexpected nature, and especially when it relates to a disease of such impact as Alzheimer’s disease”, says Professor Stefan Ståhl, who leads a research group at School of Biotechnology, KTH, that has developed the Affibody protein in collaboration with the biotech company Affibody AB.

The study provides not only the first high-resolution 3D structure of the amyloid-ß peptide bound to an aggregation-preventing agent, i.e. the Affibody® molecule, but also demonstrates how the Affibody protein embraces the peptide and thereby buries large parts of it within a tunnel-like structure. “While other molecules that interact with the amyloid-ß peptide typically also bind to the peptide aggregates, the Affibody® protein specifically binds non-aggregated, single amyloid-ß peptide molecules”, explains senior author Professor Torleif Härd. Importantly the mode of interaction explains why full inhibition of aggregation is achieved.

Successful Swedish research collaboration
Present treatments of Alzheimer’s are focused on the limiting the major symptom of the disease, i.e. memory loss. No cure or effective treatments of Alzheimer’s disease are available. The results of the research team might allow new possible strategies for treatment.

“The obtained results could have great clinical impact but further studies remain to assess whether it will give us new efficacious treatments for Alzheimer’s disease.” says Professor Bengt Winblad at the Karolinska Institute.

* Proceedings of the National Academy of Sciences of the United States of America, “Stabilization of a β-hairpin in monomeric Alzheimer’s amyloid-β peptide inhibits amyloid formation” of Wolfgang Hoyer, Caroline Grönwall, Andreas Jonsson, Stefan Ståhl, and Torleif Härd.

The article is available for subscribers: www.pnas.org