Alzheimer’s Antibodies Created to Target Harmful Proteins for Treatment Possibilities

Researchers have developed a new way to design antibodies tailored to combat disease. The simple process was used to make antibodies that neutralize the harmful protein particles that lead to Alzheimer’s disease (AD).

The process was reported in the December 5, 2011, early edition of the journal Proceedings of the [US] National Academy of Sciences (PNAS).The process could be used as a tool to understand complex disease pathology and develop new antibody-based drugs in the future.

Scientists have long searched for ways to design antibodies to fight specific disorders. However, the vast complexity of designing antibodies that only attached to a target molecule of interest has prevented scientists from realizing this ambitious objective. When attempting to design an antibody, the arrangement and sequence of the antibody loops is of vital importance. Only a very specific combination of antibody loops will bind to and neutralize each target. With billions of different possible loop arrangements and sequences, it is seemingly impossible to predict which antibody loops will bind to a specific target molecule.

The new antibody design process was used to create antibodies that target a devastating molecule in the body: the Alzheimer’s protein. The research, which was led by Rensselaer Polytechnic Institute (Troy, NY, USA) assistant professor of chemical and biologic engineering Dr. Peter Tessier, uses the same molecular interactions that cause the Alzheimer’s proteins to stick together and form the toxic particles that are a key characteristic of the disease. “We are actually exploiting the same protein interactions that cause the disease in the brain to mediate binding of antibodies to toxic Alzheimer’s protein particles,” Dr. Tessier said.

AD is due to a specific protein--the Alzheimer’s protein--sticking together to form protein particles. These particles then damage the normal, healthy functions of the brain. The formation of similar toxic protein particles is essential to diseases such as mad cow disease and Parkinson’s.

Significantly, the new Alzheimer’s antibodies developed by Dr. Tessier and his colleagues only attached on to the harmful clumped proteins and not the harmless monomers or single peptides that are not associated with disease. Dr. Tessier and his colleagues see the possibility for their technique being used to target and better determine similar types of protein particles in disorders such as Parkinson’s disease. “By binding to specific portions of the toxic protein, we could test hypotheses about how to prevent or reverse cellular toxicity linked to Alzheimer’s disease,” Dr. Tessier said.

In the long term, as scientists learn more about methods to deliver drugs into the extremely well protected brain tissue, the new antibody research may also help to develop new drugs to fight disorders such as Alzheimer’s disease.

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