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Artificial Antibody Could Prevent Harmful Protein Formation in Parkinsonís

Researchers have developed a new type of artificial antibody that stops alpha-synuclein protein (α-syn) from clumping in the test tube, according to a study in the December 4 issue of the Proceedings of the National Academy of Sciences USA. The antibodies may someday be useful in preventing or treating diseases such as Parkinson’s disease (PD) that are characterized by such proteins, called amyloids.

Amyloids are toxic clumps of proteins that can build up in people’s organs. In PD, the protein alpha-synuclein forms amyloids, which in this case are called Lewy bodies. If scientists can find a way to keep these harmful protein clumps from forming, they may be able to prevent or slow the progression of Parkinson's disease.

With this goal in mind, researchers led by Peter Tessier, Ph.D., at the Rensselaer Polytechnic Institute engineered a new type of antibody that prevents amyloid protein clumps from forming. In contrast to natural antibodies produced by the immune system, these antibodies were made in the lab. The antibodies contained short stretches of the amyloid protein that targeted α-syn and other amyloids. Dr. Tessier and his colleagues named these new antibodies gammabodies, and studied their effectiveness in test tubes.

Results

  • Gammabodies designed to target α-syn proteins did prevent the proteins from clumping.
  • Only small amounts of the gammabodies were required to prevent the proteins from clumping.
  • The gammabodies worked primarily by gathering the proteins into small, harmless clumps so that they couldn’t assemble into larger amyloids.
  • The gammabodies prevented amyloid formation better than natural antibodies produced by immunization.

What Does It Mean?

Protein clumps called amyloids have been detected in people with Parkinson’s and other diseases. In PD, researchers think that these clumps, called Lewy bodies, cause or at least contribute to symptoms of the disease. Strategies to keep Lewy bodies from forming may help prevent or treat PD.

Dr. Tessier and his colleagues, inspired by the ability of the body’s natural antibodies to prevent harm from bacteria and viruses, designed and produced artificial antibodies that target disease-causing proteins and keep them from forming clumps.

Although gammabodies will likely be useful tools for research, much more work needs to be done before they could be tested as a therapy for PD and other diseases. The experiments in this study were conducted in test tubes, a very different environment from the human body. The researchers do not yet know if gammabodies are safe and effective for people, how doctors could administer them (for example, by pill or injection), or if they could pass from the bloodstream into the appropriate organ (in PD, the brain). Future studies using animal models should help answer some of these questions.

Reference: Ladiwala, A. R., Bhattacharya, M., Perchiacca, J. M., Cao, P., Raleigh, D. P., Abedini, A., Schmidt, A. M., Varkey, J., Langen, R., & Tessier, P. M. (2012). Rational Design of Potent Domain Antibody Inhibitors of Amyloid Fibril Assembly. Proc. Natl. Acad. Sci. USA, 109(49), 19965–19970. doi: 10.1073/pnas.1208797109

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Source Date: Jan 14 2013